Martin G. Radvany

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.

Visual and neurological outcomes following endovascular stenting for pseudotumor cerebri associated with transverse sinus stenosis

Background: Pseudotumor cerebri (PTC) is characterized by raised intracranial pressure (ICP) without an identifiable mass, evidence of hydrocephalus, or abnormal cerebrospinal fluid content. In the past, most cases of PTC appeared to have no identifiable etiology, and thus, they were classified as “idiopathic intracranial hypertension” (IIH). Recently, however, a subset of patients with presumed IIH has been found to have evidence of cerebral dural sinus stenoses, particularly involving one or both transverse sinuses (TS). The belief that the stenoses are the cause, rather than an effect of the increased ICP, has led investigators to recommend stenting of the stenosed sinus for the treatment of the condition. We describe detailed visual and neurological outcomes after stenting for PTC associated with hemodynamically significant dural sinus stenosis. Methods: All patients with PTC had initial neurological, neuro-ophthalmological, and imaging assessments. Regardless of the findings, all were treated with medical therapy. If medical therapy failed and TS stenosis was detected on contrast-enhanced magnetic resonance or computed tomographic venography, catheter cerebral angiography with venous manometry was performed. If a mean pressure gradient (MPG) of 4 mm Hg or greater was present, unilateral transverse sinus stenting was performed. Results: Twelve patients with PTC and TS stenosis associated with an MPG of >4 mm Hg who failed medical therapy were identified. TS stenting significantly decreased the pressure gradient in all cases. Unilateral stenting was sufficient to reduce pressure gradients even when the stenosis was bilateral. At a mean follow-up of 16 months (range, 9–36 months), tinnitus had improved in all patients, and 10 of 12 patients had improvement in visual function. Seven patients had significant improvement in headaches. Conclusion: In this small series of patients with PTC associated with TS stenosis, endovascular stent placement was generally effective in treating visual dysfunction and tinnitus, although not headaches. The optimum gradient and vascular characteristics amenable for selection of patients for stenting needs further research.

Initial Experience with a Handheld Device Digital Imaging and Communications in Medicine Viewer: OsiriX Mobile on the iPhone

Medical imaging is commonly used to diagnose many emergent conditions, as well as plan treatment. Digital images can be reviewed on almost any computing platform. Modern mobile phones and handheld devices are portable computing platforms with robust software programming interfaces, powerful processors, and high-resolution displays. OsiriX mobile, a new Digital Imaging and Communications in Medicine viewing program, is available for the iPhone/iPod touch platform. This raises the possibility of mobile review of diagnostic medical images to expedite diagnosis and treatment planning using a commercial off the shelf solution, facilitating communication among radiologists and referring clinicians.

A single center comparison of coiling versus stent assisted coiling in 90 consecutive paraophthalmic region aneurysms

Introduction Aneurysm recurrence is a principle limitation of endovascular coiling procedures, with recurrence rates reported of >30%. The adjunct use of self-expandable stents has revolutionized the treatment of intracranial aneurysms, especially for complex morphologies, wide necks or unfavorable dome to neck ratios. However, further investigation into the durability and outcomes of stent assisted coiling procedures is required. Methods The records of a prospective single center aneurysm database were retrospectively reviewed, and 90 consecutive patients with paraophthalmic aneurysms who underwent coil embolization were identified, 30 of which included stent placement. Patient demographics, aneurysm characteristics, coil packing density, angiographic results (initial and follow-up) and complications were analyzed. Results Complete aneurysm occlusion was obtained on initial angiography in 13/30 (43.3%) stented and 19/60 (31.7%) non-stented patients. At ≤24 months (mean follow-up 12.8±6.2 months for stented and 12.8±6.6 months for non-stented group), aneurysm recurrence occurred in 3/26 (11.5%) stented and 14/39 (35.9%) non-stented patients (p<0.05). At the longest follow-up (mean 14.5±12.5 months for stented and 37.6±35.3 months for non-stented), aneurysm recurrence occurred in 4/26 (15.4%) stented and 17/41 (41.5%) non-stented patients (p<0.03). There was no statistically significant correlation between recurrence and aneurysm size or coiling packing. Conclusions Following endovascular coil embolization of paraophthalmic region aneurysms, recurrence rates at 2 years were significantly lower in patients who had stent assisted coiling (11.5%) compared with patients who had coiling procedures without the use of a stent (35.9%). Aneurysm size and coiling packing density did not significantly affect recurrence in our study population.

Plaque Excision in Management of Lower Extremity Peripheral Arterial Disease with the SilverHawk Atherectomy Catheter.

Atherectomy, the removal of plaque from diseased vessels, is theoretically appealing with respect to various procedures used for revascularization of lower extremity vessels. Instead of damaging the native vessel by pushing aside plaque with a balloon or stent, the plaque is removed. Many atherectomy devices have been designed in attempts to achieve this goal. The SilverHawk device is the latest percutaneous device employing this treatment strategy. We discuss patient selection, technical considerations, and strategies for both above and below the knee revascularization, as well as pitfalls in each location based on our experience with over 200 patients.

Venous sinus stenting is a valuable treatment for fulminant idiopathic intracranial hypertension

Over the past 10 years, transverse sinus stenting has grown in popularity as a treatment for idiopathic intracranial hypertension. Although promising results have been demonstrated in several reported series, the vast majority of patients in these series have been treated on an elective basis rather than in the setting of fulminant disease with acute visual deterioration. We identified four patients who presented with severe acute vision loss between 2008 and 2012 who were treated with urgent transverse sinus stenting with temporary cerebrospinal fluid (CSF) diversion with lumbar puncture or lumbar drain as a bridge to therapy. All patients presented with headache, and this was stable or had improved at last follow-up. Three patients had improvement in some or all visual parameters following stenting, whereas one patient who presented with severe acute vision loss and optic disc pallor progressed to blindness despite successful stenting. We hypothesize that she presented too late in the course of the disease for improvement to occur. Although the management of fulminant idiopathic intracranial hypertension remains challenging, we believe that transverse sinus stenting, in conjunction with temporary CSF diversion, represents a viable treatment option in the acute and appropriate setting.

Enhanced Visualization Processing: Effect on Workflow

RATIONALE AND OBJECTIVES Soft-copy viewing of digital radiographs allows for image processing to improve visualization of anatomy and lesions, but it can take more time than film-based viewing. Enhanced visualization processing (EVP) was developed to increase the latitude of an image without reducing the vital contrast, potentially reducing the need for the radiologist to manipulate images. This study examined the influence of processing radiographic images with EVP on workflow in a picture archiving and communications system (PACS). MATERIALS AND METHODS Portable computed radiographic chest images were obtained and processed either with EVP or without. A security camera with a videocassette recorder was positioned above the PACS workstation. Four radiologists reviewed the images during their normal work schedule. The current diagnostic image was used to determine if the case contained EVP or non-EVP images. The videotapes of the sessions were reviewed to determine diagnostic viewing times and how zoom and/or window and level manipulation was used. RESULTS Viewing time was significantly longer for the non-EVP than the EVP cases. The difference occurred with all readers. Window and level manipulation was used on 35% of the EVP and 41% of the non-EVP images. Zoom was used on 64% of the EVP and 69% of the non-EVP images. Average time spent using zoom and window and level manipulation was significantly shorter with the EVP than with the non-EVP images. CONCLUSION EVP of chest images displayed on PACS monitors significantly improved workflow as measured by viewing time. EVP decreased use of window and level manipulation and zooming and the amount of time each one was used.

Endovascular Management of Neurovascular Arterial Injuries in the Face and Neck

The diagnosis and treatment of traumatic vascular injuries continues to improve as new tools and techniques are developed. In addition to locoregional hemorrhagic complications, injuries to blood vessels in the neck and face can result in ischemic injuries to the brain and cervical spinal cord. Surgical access to these lesions may be difficult, and endovascular techniques, including stenting and embolization, now serve as definitive treatments in many instances. This article reviews the endovascular management of patients with arterial injuries in the neck and face.

Impact of indocyanine green videoangiography on rate of clip adjustments following intraoperative angiography.

BACKGROUND Intraoperative angiography (IA) is used to evaluate the adequacy of clip reconstruction of intracranial aneurysms. Alternative imaging such as indocyanine green videoangiography (ICG-VA) has been proposed. The additional benefit of ICG-VA when IA is routinely used has not been previously determined. OBJECTIVE To report our experience with the use of ICG-VA in combination with IA vs IA alone. METHODS We retrospectively reviewed cases of aneurysm clipping during a 21-month period by a single surgeon in which ICG-VA was performed after clip reconstruction prior to IA, or IA alone was performed to verify optimal clipping. Records were reviewed for age, sex, race, length of stay, rupture status, Hunt and Hess grade, aneurysm size, location, and temporary clipping. Intraoperative decision making was determined for each group. RESULTS Ninety-four patients who underwent 97 craniotomies for 128 aneurysms met inclusion criteria for this study. ICG-VA+IA was performed in 37 craniotomies; IA alone was performed for 60 craniotomies. Baseline characteristics were similar with the exception that median aneurysm size was slightly larger in the ICG-VA group (5.6 mm vs 4.3 mm, P = .04). ICG-VA produced 4 false negatives, which required clip adjustments following IA (10.8%), vs 7 patients (11.7%) in the IA-alone group requiring clip adjustments (P = .897). CONCLUSION When IA is routinely performed, the additional use of ICG-VA does not eliminate the need for post-IA clip adjustments owing to the possibility of false negatives. When ICG-VA suggests optimal clipping, but is followed by IA, the rate of post-IA modifications in this study did not differ significantly than if ICG-VA had not been performed.

Risk factors for failed transverse sinus stenting in pseudotumor cerebri patients

BACKGROUND Idiopathic intracranial hypertension (IIH) when no underlying etiology is found, is a clinical syndrome characterized by elevated intracranial pressure (ICP) (>25 cm H2O), which may lead to headaches and visual symptoms. In patients with IIH who are found to have transverse sinus stenosis, placement of a venous stent across the stenosis has been shown to lower ICP and to resolve the symptoms in several case series, with generally favorable results. In this study, we examine common risk factors associated with failure of transvenous stenting for IIH. If venous sinus stenting fails, CSF diversion should be considered as the next line of treatment. METHODS We retrospectively reviewed the records of eighteen patients diagnosed with IIH who underwent venous sinus stenting for transverse sinus stenosis with a mean pressure gradient (MPG) of at least 4 mmHg. Fifteen of these patients did not need further treatment. We compared their pre- and post-treatment, neurological and neuro-ophthalmological evaluations to the three patients who went on to have a shunt placement as a second line treatment. RESULTS Shunting after stent placement patients (n=3) had a mean age of 30 years and a mean body mass index of 36.6 kg/m(2), whereas the group that underwent stent placement alone (n=15) had a mean age of 40.7 years and a mean body mass index of 33.3 kg/m(2). In the shunting after stent placement group, the mean opening pressure on the most recent lumbar puncture obtained prior to any intervention was 50 cm of H2O, whereas the group that underwent stent placement alone had an opening CSF pressure of 37 cm of H2O which was statistically significant (p<0.05). There were no other significant differences in pre- or post-intervention factors between the two groups. CONCLUSION In patients with IIH and documented evidence of venous sinus stenosis with a pressure gradient, venous sinus stenting should be the primary treatment of choice; however, some patients may be refractory to stenting and still require permanent CSF diversion, which can be complicated in these chronically anticoagulated patients. Patients with persistent papilledema post-stenting and highly elevated opening pressure pre-stenting should be followed closely as they are at greatest risk of requiring a shunt and failing stenting.