Unfavorable Natural History Research Articles

Strategic Dual Approach for the Management of a Symptomatic Giant Partially Thrombosed Aneurysm at the Basilar Tip - Integrating Intrasaccular Flow Diversion and Endovascular Flow Reversal.

Managing giant partially thrombosed intracranial aneurysms presents significant challenges due to their unfavorable natural history and the lack of standardized treatment approaches. Conventional treatments, whether open surgical or endovascular, often struggle to manage these aneurysms effectively, resulting in high recurrence rates or significant morbidity. The patient was a 62-year-old male with a symptomatic giant partially thrombosed aneurysm at the tip of the basilar artery, presenting with left-sided hemiparesis and dysarthria. Diagnostic imaging revealed a giant aneurysm with a wide-necked, canalized portion. A two-stage endovascular treatment was conducted, involving a balloon occlusion test (BOT) and intraoperative monitoring (IOM) for maximum patient safety. The treatment utilized stent-assisted Woven EndoBridge (WEB) embolization and serial bilateral vertebral artery trapping. The procedure successfully isolated the aneurysm and postoperative imaging confirmed the absence of recanalization, preserving the intact posterior circulation. The patient showed stable recovery and no neurological deficits during the 12-month follow-up period. This technical note demonstrates the feasibility and efficacy of strategically integrating intrasaccular flow diversion using a WEB device and flow reversal through bilateral vertebral artery trapping for treating giant partially thrombosed aneurysms.

Fourth-generation bypass and flow reversal to treat a symptomatic giant dolichoectatic basilar trunk aneurysm.

Giant dolichoectatic basilar trunk aneurysms have an unfavorable natural history and are associated with high morbidity, but their neurosurgical treatment is complex and challenging. Flow reversal reconstruction with fourth-generation bypass and proximal vertebral artery clip occlusion is performed via orbitozygomatic craniotomy with the Kawase approach under rapid ventricular pacing. Fourth-generation bypass is an innovative, technically challenging, and clinically effective tool in the treatment armamentarium for giant dolichoectatic basilar trunk aneurysms.

Alport syndrome: our knowledge update

Alport syndrome is a progressive multisystem disease associated with variants in genes COL4A3, COL4A4, COL4A5.The syndrome is an important genetic cause of kidney failure, including women with X-linked disease. Given the unfavorable natural history of Alport nephropathy and benefit from early treatment with angiotensin-converting enzyme inhibition, it is necessary to change our diagnostic approach in patients with persistent glomerular hematuria and management of patients with Alport syndrome. This review presents the ethiology, pathogenesis, genotype and phenotype heterogeneity of the syndrome and expert clinical practice recommendations to enhancing early diagnosis and achieving optimal outcomes in Alport syndrome.

Unfavorable Outcomes Related to Endovascular Treatment of Giant Vertebrobasilar Aneurysms.

Background: Giant vertebrobasilar aneurysms (GVBAs) have an unfavorable natural history if left untreated and often pose a sizeable challenge to endovascular treatment. The aim of this study was to analyze the angiographic and clinical outcomes of GVBAs treated by various endovascular procedures.Methods: Between January 2010 and September 2018, 27 patients with 27 GVBAs treated endovascularly were enrolled in this consecutive study. The clinical and angiographic features, treatment modalities, and outcomes were analyzed.Results: The patient cohort comprised 21 men (77.8%) and 6 women (22.2%) of mean age 42.7 ± 18.9 years (range, 6–65 years). The most common presenting symptom was compressive symptoms, present in 15 patients (55.6%). None of the GVBAs was ruptured. Of the 27 GVBAs, 23 aneurysms were dissecting aneurysm with intramural hematoma and 4 aneurysms were saccular. Regarding treatment approach, internal trapping was used in 5 aneurysms, stent-assisted coil embolization in 10, sole stenting in 4, and flow diverters in 8. Overall, 12 patients (44.4%) had an unfavorable angiographic or clinical outcome: 3 patients presented with post-operative complications and subsequent death, and 9 with poor prognosis during follow-up.Conclusions: Patients with GVBAs may not benefit from endovascular treatment. Newer-generation devices are necessary to provide more optimal therapy for the management of these complex lesions.

Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review.

Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility criteria included patients 16 years of age and older, notation of LGG subtype, and report of progression-free survival (PFS), overall survival (OS), and treatment course. Level I, II, and III data were included. Adjuvant therapy with PCV resulted in prolonged PFS and OS in patients with newly diagnosed high-risk LGG. This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation. Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV. In patients with LGG with an unfavorable natural history, such as with intact 1p/19q and wild-type IDH1, RT/TMZ plus adjuvant TMZ may be the best option. Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV.

The challenge of preoperative quantification of functional tricuspid regurgitation and of right ventricle function: what information is clinically relevant?

Functional or secondary tricuspid regurgitation (TR) is the most common etiology of severe TR in the western world. The presence of functional TR, either isolated or in combination with left heart disease is associated with unfavorable natural history however surgical mortality for isolated tricuspid valve interventions remain higher than for any other single valve surgery. Determining the severity of TR remains a controversial area and will continue to evolve as new techniques for assessing this valve as well as the right ventricle, are investigated. The following review will describe tricuspid anatomy, define echocardiographic views for evaluating tricuspid valve and right heart morphology and function, that are relevant to the pre-procedural assessment of functional TR.

State-of-the-Art Review of Echocardiographic Imaging in the Evaluation and Treatment of Functional Tricuspid Regurgitation.

Functional or secondary tricuspid regurgitation (TR) is the most common cause of severe TR in the Western world. The presence of functional TR, either isolated or in combination with left heart disease, is associated with unfavorable natural history. Surgical mortality for isolated tricuspid valve interventions remains higher than for any other single valve surgery, and surgical options for repair do not have consistent long-term durability. In addition, as more patients undergo transcatheter left valve interventions, developing transcatheter solutions for functional TR has gained greater momentum. Numerous transcatheter devices are currently in early clinical trials. All patients require an assessment of valve morphology and function, and transcatheter devices typically require intraprocedural guidance by echocardiography. The following review will describe tricuspid anatomy, define echocardiographic views for evaluating tricuspid valve morphology and function, and discuss imaging requirements for the current transcatheter devices under development for the treatment of functional TR.

Therapeutic progress in pediatric intracranial dural arteriovenous shunts: A review.

Pediatric dural arteriovenous shunts (dAVSs) are a rare form of vascular disease: Fewer than 100 cases are reported in PubMed and the understanding of pediatric dAVS is limited. For this study, we searched in PubMed, reviewed and summarized the literature related to pediatric dAVSs. Our review revealed that pediatric dAVSs have an unfavorable natural history: If left untreated, the majority of pediatric dAVSs deteriorate. In a widely accepted classification scheme developed by Lasjaunias et al., pediatric dAVSs are divided into three types: Dural sinus malformation (DMS) with dAVS, infantile dAVS (IDAVS) and adult-type dAVS (ADAVS). In general, the clinical manifestations of dAVS can be summarized as having symptoms due to high-flow arteriovenous shunts, symptoms from retrograde venous drainage, symptoms from cavernous sinus involvement and hydrocephalus, among other signs and symptoms. The pediatric dAVSs may be identified with several imaging techniques; however, the gold standard is digital subtraction angiography (DSA), which indicates unique anatomical details and hemodynamic features. Effectively treating pediatric dAVS is difficult and the prognosis is often unsatisfactory. Transarterial embolization with liquid embolic agents and coils is the treatment of choice for the safe stabilization and/or improvement of the symptoms of pediatric dAVS. In some cases, transumbilical arterial and transvenous approaches have been effective, and surgical resection is also an effective alternative in some cases. Nevertheless, pediatric dAVS can have an unsatisfactory prognosis, even when timely and appropriate treatment is administered; however, with the development of embolization materials and techniques, the potential for improved treatments and prognoses is increasing.

Aneurysms Associated with Brain Arteriovenous Malformations.

Brain arteriovenous malformations are frequently associated with the presence of intracranial aneurysms at a higher-than-expected incidence based on the frequency of each lesion individually. The identification of intracranial aneurysms in association with AVMs has increased due to improvement in diagnostic techniques, particularly 3D and superselective conventional angiography. Intracranial aneurysms may confer a higher risk of hemorrhage at presentation and of rehemorrhage in patients with AVMs and therefore may be associated with a more unfavorable natural history. The association of AVMs and intracranial aneurysms poses important therapeutic challenges for practicing neurosurgeons, neurologists, and neurointerventional radiologists. In this report, we review the classification and radiology of AVM-associated intracranial aneurysms and discuss their clinical significance and implications for treatment.

Treatment of patients with mild acute ischemic stroke and associated large vessel occlusion

Several recent studies have shown that patients presenting with mild acute ischemic stroke (mAIS) symptoms may have an unfavorable natural history. The presence of associated large vessel occlusion (LVO) may lead to even worse outcomes, but most mAIS patients are still excluded from acute stroke treatment (AST). A retrospective review of patients with acute ischemic stroke presenting to our institution between 2010 and 2014 was carried out. Inclusion criteria were mAIS (initial National Institutes of Health Stroke Scale [NIHSS] ⩽7) due to LVO, presenting within 6hours from onset. Demographics, treatments and short-term outcomes were analyzed. Favorable 30day outcome was defined as modified Rankin Scale (mRS) ⩽2. Out of 2636 patients, 62 patients (median age 63years, 33 (53.2%) males) met inclusion criteria. The anterior circulation was involved in 74.1%. Median admission NIHSS and pre-admission mRS were 4 and 0, respectively. Twenty-three patients (71.8%) received AST (intravenous tissue plasminogen activator: 14, intra-arterial therapy: 4, both: 5). Favorable outcomes were 4.5 times higher in treated (78.3%) versus untreated (53.8%) patients (odds ratio 4.5, 95% confidence interval 1.26–19.2; p=0.028). None of the treated patients had symptomatic intracranial hemorrhage. We demonstrate that a significant proportion of untreated mAIS patients with LVO have an unfavorable natural history. Our results suggest better outcomes in patients who receive early therapy rather than conservative management. The detection of LVO, even with mild clinical symptoms, may prompt rapid treatment considerations.

Anterior approaches for cervical spondylotic myelopathy: which? When? How?

Cervical spondylotic myelopathy is a degenerative disorder with an unfavorable natural history. Surgical treatment options have evolved substantially over time, with both anterior and posterior methods proving successful for certain patients with specific characteristics. Anterior decompression of the spinal canal plus fusion techniques for stabilization has several advantages and some disadvantages when compared to posterior options. Understanding the pros and cons of the approaches and techniques is critical for the surgeon to select the best operative treatment strategy for any given patient to achieve the best outcome. Multiple decision-making factors are involved, such as sagittal alignment, number of levels, shape of the pathoanatomy, age and comorbidities, instability, and pre-operative pain levels. Any or all of these factors may be relevant for a given patient, and to varying degrees of importance. Choice of operative approach will therefore be dependent on patient presentation, risks of that approach for a given patient, and to some degree surgeon experience.

Oral and sublingual peanut immunotherapy is not ready for general use

Food oral immunotherapy (OIT) is an investigational peanut allergy treatment aimed to achieve specific oral tolerance induction. Allergic children are given titrated oral (or sublingual) doses of their allergen on a daily basis, unlike in subcutaneous immunotherapy (SCIT). OIT is theorized to cause a shift from a Th2 to a Th1 regulatory environment, reflected by increases in food-specific IgG4/IgE, and the production of FoxP3. Peanut OIT holds special promise because peanut allergy has an unfavorable natural history and is rarely outgrown. A high percentage of the participants experience symptoms during peanut OIT, including anaphylaxis, warranting epinephrine and/or discontinuation of therapy. This is a concerning fact given that the studies have mostly targeted only older children, with less historical reactivity for enrollment. The handful of peanut OIT studies have shown that some participants can be desensitized to peanut, but none have shown that long-term tolerance can be reestablished. Factors predictive of which patients are most likely to succeed and become desensitized through OIT are unknown. Some private practices have begun offering peanut OIT as a therapy. Such practice is potentially dangerous given the safety and efficacy of OIT in randomized controlled clinical trials is still not well established. Therefore, until further investigation emerges that conclusively demonstrates OIT is safe, intermediate and long-term outcomes are better established, the number of participants that experience symptoms is reduced, and proof of concept established in patients of all ages, (irrespective of past reaction severity), OIT is not ready for use in the general allergy practice.

Mycotic Aortic Aneurysm Caused by Haemophilus influenzae Group F

Haemophilus influenzae is a rare cause of mycotic aortic aneurysm. We present a case of H. influenzae mycotic aortic aneurysm, which was complicated by prior endovascular stent-graft placement at another facility. A 58 year-old man was treated by endograft placement for a presumed penetrating aortic ulcer after having symptoms of abdominal pain and malaise for one month. He presented to our institution 11 days after endograft placement with septic physiology. Repeat computed tomography angiogram demonstrated an inflammatory mass around the distal aorta and right common iliac artery, which had an associated contained rupture. The patient was treated using intravenous antibiotics, axillo-bifemoral bypass followed by endograft explantation and aortic and iliac ligation. Intraoperative cultures grew Haemophilus influenzae, serotype f. Aortic endografts have been successfully used for treatment of selected mycotic aneurysms, generally after adequate treatment of the primary infection with intravenous antibiotics. This case demonstrates the unfavorable natural history of endograft placement in an unsuspected mycotic aneurysm. A high index of suspicion for possible aortic infection should be maintained for patients with systemic symptoms and unusual aortic pathology prior to choosing endovascular repair.

The role of the Fontan operation in the treatment of congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries (ccTGA) is a complex cardiac anomaly with an unfavorable natural history. Surgical treatment has been available for over 50 years. Initial procedures used for ccTGA did not correct atrio-ventricular discordance, leaving the right ventricle in systemic position. In the past two decades anatomic repair has been considered to be a better option. Many cases subjected to anatomic repairs would also be suitable for the Fontan strategy, which probably has a lower initial risk. The rationale for use of the Fontan operation in management of congenitally corrected transposition is discussed in this review, with comparisons to other strategies.

Disruption of the ASXL1 Gene Is Prevalent In PMF: Analysis of Molecular Genetics and Clinical Phenotypes

AbstractAbstract 3074 Background:The myeloproliferative neoplasms, PV, ET and PMF, share phenotypic features and molecular lesions, yet PMF distinguishes itself by its unfavorable natural history and rate of leukemic evolution. These distinctions may occur as a result of cooperating genomic lesions specific to PMF compared to PV or ET. We performed single nucleotide polymorphism array (SNP-A)-based karyotyping in 210 MPN patients and identified 20q11 deletions in 10% of PMF cases and in none of the PV or ET cases. The 20q11 deletion region spanned 1,662 KB and encompassed 37 genes, of which ASXL1 was included. To test whether ASXL1 contained lesions in the MPN cohort at large, we directly sequenced key regions of the ASXL1 gene in 65 PMF, 11 PV and 14 ET cases, as well as 7 controls from the SNP-array cohort. Genomic DNA from neutrophils and in select cases, purified CD34+ cells was used for both SNP-A and direct sequencing. Clinical parameters were correlated with genomic findings and the quantitative JAK2 V617F neutrophil allele burden Molecular genetics:26/65 (40%) of PMF cases had abnormalities in ASXL1 (4 deletions, 22 mutations) whereas none of the 32 PV, ET or control cases had such lesions. The majority of ASXL1 sequence variations were nonsense lesions including the previously reported 1934dupG which comprised 30% of all of the mutations. The residual ASXL1 allele in all 20q11 deletion cases containing the ASXL1 gene was intact. In three PMF cases, more than one distinct ASXL1 mutation was identified, and cloning experiments on two of those cases indicated that the lesions were biallelic. Using banked samples, we observed the acquisition of an ASXL1 lesion over time, and established that ASXL1 lesions detected in 2 post ET-MF cases were also detected at low levels in the ET phase of the MPN. Genotype/Phenotype Correlations:ASXL1 deletions and mutations were prevalent in de novo PMF (37%), post PV-PMF (20%) post ET-PMF (62%) and in PMF/AML (33%). ASXL1 mutations did not associate with chemotherapy exposure as the prevalence of hydroxyurea use was similar in patients with and without mutations, and ASXL1 –mutation positive cases were present in patients who had never received any form of chemotherapy. There was no dependence upon JAK2 status as the presence of ASXL1 mutations were identified in JAK2 V617F-negative cases (9/26); JAK2 V617F-heterozygous cases (10/26); and JAK2 V617F-homozygous cases (7/26). Based on results of SNP-A, patients with ASXL1 mutations were equally as likely to have uniparental disomy (involving 9p or other regions) and loss/gain abnormalities (>1MB) compared to those without ASXL1 mutations. There were no differences in sex, age, or disease duration between PMF patients with and without ASXL1 mutations. In the ASXL1-mutant group, there was a trend toward a lower median white blood cell count (8 vs. 12.5 k/cu mm; p=0.3) and hemoglobin (9.7 vs. 11 g/dl; p=0.3) compared to ASXL1-wild-type patients. Furthermore, those PMF patients with ASXL1 mutations were significantly more likely to have received anemia-directed therapy (transfusion, erythropoietin, immunomodulating agents, steroids) compared to those without mutations (15/26 (58%) vs. 11/39 (23%); p=0.02). Post ET-MF patients comprised 31% (8/26) of ASXL1-mutant cases, compared to only 10% (4/39) ASXL1- wild-type cases (p=0.03). However, the presence of an ASXL1 mutation did not associate with an accelerated transition rate from ET to MF; among the 12 post ET-MF cases in the cohort, the median time of transition from ET to MF was 15.5 years in those with ASXL1 mutations compared to 7 years in those with ASXL1 wild-type status (p=0.02). Conclusion:Disruption of the ASXL1 gene occurs in 40% of PMF cases. The association of ASXL1 lesions, due to either mutation or deletion, suggests that ASXL1 haplo-insufficiency is associated with a PMF phenotype in the context of other known and unknown lesions, and that disruption of ASXL1 function may directly contribute to the pathophysiology and clinical complications of primary and secondary myelofibrosis. These data support the concepts that cooperative lesions in addition to JAK2 V617F are critical in generating PMF, that PMF is molecularly more complex than either PV or ET, and that the transition of PV or ET to PMF is associated with the acquisition of genomic lesions, such as ASXL1, that are present in PMF at large. Disclosures:No relevant conflicts of interest to declare.

Efficacy of Aggressive Lipid Controlling Therapy for Preventing Saphenous Vein Graft Disease

Conclusion: Aggressive lipid-controlling therapy may be effective in preventing saphenous vein graft disease after coronary artery bypass grafting (CABG). Summary: About 25% of saphenous vein grafts occlude ≤1 year of CABG, and 50% occlude ≤ 10 years (Am Heart J 1990;119:1164-84). Despite their relative unfavorable natural history, saphenous vein grafts are still used in >70% of CABG procedures. It appears that plaque rupture with thrombus formation are a major cause of long-term saphenous vein graft disease after CABG (Circulation 2007;71:286-7). It also appears that lowering low-density lipoprotein cholesterol (LDL-C) <100 mg/dL may be effective in reducing atherosclerosis in saphenous vein grafts. In this study, the authors sought to investigate the efficacy of aggressive statin therapy on angioscopic-determined progression of saphenous vein graft disease after CABG. There were 21 patients after CABG divided into two groups. Group I comprised 10 patients whose serum LDL-C levels and LDL/high-density lipoprotein (HDL) ratios could be controlled to <80 mg/dL and <1.5, respectively. Group II consisted of 11 patients whose LDL-C levels and LDL/HDL ratios were >100 mg/dL and >2.5, respectively. Twenty-seven saphenous vein grafts were assessed by intravascular ultrasound (IVUS) and angioscopy at 12 to 16 months postoperatively. Serum LDL-C levels in group I were 64.1 vs 130.2 mg/dL in group II. LDL/HDL ratios in group I were 1.36 vs 2.64 in group II. High-sensitivity C-reactive protein in group I was 0.045 ± 0.1 vs 0.116 ± 0.02 mg/dL in group II. All values were significantly lower in group I. In group II, IVUS detected eccentric plaques in 11 of 14 saphenous vein grafts (78.6%). Yellow plaque was present in all 14 saphenous vein grafts by angioscopy, and 11 of these grafts had thrombi. The 13 saphenous vein grafts in group I had no eccentric or yellow plaques, and no thrombi were visible. The intima was entirely clear white. Comment: The mechanism of failure of saphenous vein grafts in the coronary circulation may be different than that in the peripheral circulation. However, the idea that driving down LDL-C and C-reactive protein levels may improve vein graft patency is intriguing for the peripheral vascular surgeon as well. Indeed, there is evidence suggesting higher primary assisted and secondary patency in lower extremity vein grafts in patients treated with statins (J Vasc Surg 2004;39:1178-85). Well-designed prospective data are needed to assess the effects of statins on suppression of peripheral vein graft lesions.

Mitral Valve Repair: What the ACORN Trial Taught Us

Progressive left ventricular remodeling is characterized by dilation of the left ventricle with a change in the heart from an elliptical shape to a more spherical shape. This change is part of the unfavorable natural history in patients with heart failure. The CorCap Cardiac Support Device (Acorn Cardiovascular, St. Paul, MN) is a mesh device that is implanted around the heart to reduce wall stress and the first therapy specifically designed to address left ventricular remodeling. The CorCap was studied in a large, prospective, randomized, multicentered trial. This study demonstrated safety and effectiveness of the CorCap in patients with advanced heart failure and remodeled ventricles. Moreover, it provided interesting insights into mitral valve surgery in patients with heart failure. These insights and a review of the ACORN (Assessment of a Cardiac Support Device [CSD] in Patients With Heart Failure) trial are discussed in this article.

RETINAL ANGIOMATOUS PROLIFERATION

To investigate the natural history and visual outcome in eyes with untreated retinal angiomatous proliferation, a neovascular form of age-related macular degeneration. Fourteen consecutive white patients (11 women, 78%; mean age, 74 years) with 16 eyes affected by retinal angiomatous proliferation were prospectively followed-up without treatment by means of complete ophthalmologic examinations at regular intervals, including best-corrected visual acuity and dynamic fluorescein and indocyanine green angiography using a scanning laser ophthalmoscope. The patients were observed for a mean of 20 months (range, 6-44 months). Mean visual acuity in the eyes with retinal angiomatous proliferation was 0.48 at the initial examination, decreased to 0.23 after 6 months, and was 0.19 at the final examination, with a mean decrease of 6 lines from baseline. In 13 eyes (81%), visual acuity deteriorated by 2 Early Treatment Diabetic Retinopathy Study lines or worse by the time of the 6-month examination, and 31% of the patients had experienced severe loss of vision; the remaining 3 eyes (19%) showed a relatively stable clinical course and visual acuity. By the time of the final examination, visual acuity had decreased to 0.1 or worse in 11 eyes (69%), and 5 of the 14 patients (36%) were legally blind. At the final examination, 10 eyes (62%) showed a subretinal fibrosis and 9 (56%) showed a retinal choroidal anastomosis. Retinal angiomatous proliferation is a distinct form of neovascular age-related macular degeneration with high vasogenic potential, having its own clinical course and visual prognosis. The poor visual outcome is because of the exudative nature of the retinal angiomatous proliferation, and progression to poor vision is common and rapid (within 3 months in faster cases, and within 1 year in slower cases). The treatment options for this type of neovascular lesion should be planned bearing in mind its unfavorable natural history.

The Utility of Serial Computed Tomography Imaging of Blunt Splenic Injury: Still Worth a Second Look?

Serial computed tomography (CT) imaging of blunt splenic injury (BSI) can identify the latent formation of splenic artery pseudoaneurysms (PSAs), contributing to improved success in splenic salvage. The practice of serial CT imaging, however, has not been embraced. The purpose of this study was to reevaluate the clinical practice of serial CT imaging within the context of an institutional protocol for the nonoperative management (NOM) of BSI. Consecutive patients with BSI selected for NOM were identified from our trauma registry. Patients were managed according to protocol, whereby hemodynamically stable patients with PSA on initial or follow-up CT imaging were referred for angiography. Follow-up CT was performed 24 to 48 hours after the initial CT. Data were abstracted from hospital, clinic, and radiology records, and included age, Injury Severity Score, splenic injury grade (SIG), and CT findings. The incidence and timing of PSA identification with respect to subsequent management and outcome were reviewed. Of 426 BSI admissions during a 2.5-year period, 341 (80%) were selected for NOM. Mean follow-up was 39 days, with 76% followed for >or=7 days. Serial CT imaging resulted in the angiographic detection of 14 (4%) early PSAs and 11 (3%) latent PSAs. PSAs were associated with increasing SIG (p<0.001); however, 24% of PSAs were observed in SIG 1 and 2. Embolization was successful in 13 of 14 (93%) patients with early PSAs and 10 of 11 (91%) with latent PSAs. The splenic salvage rate for all patients selected for NOM during the study period was 329 of 341 (97%). Adherence to a NOM protocol guided by serial CT imaging has resulted in one of the highest splenic salvage rates reported to date. Identification and embolization of latent PSA likely contributes to NOM success, given the unfavorable natural history of these lesions. Although PSA formation is correlated with increasing SIG, PSAs are not exclusive to higher-grade injury, warranting serial CT surveillance regardless of SIG.

Multisession CyberKnife Radiosurgery for Intramedullary Spinal Cord Arteriovenous Malformations

Intramedullary spinal cord arteriovenous malformations (AVMs) have an unfavorable natural history that characteristically involves myelopathy secondary to progressive ischemia and/or recurrent hemorrhage. Although some lesions can be managed successfully with embolization and surgery, AVM size, location, and angioarchitecture precludes treatment in many circumstances. Given the poor outlook for such patients, and building on the successful experience with radiosurgical ablation of cerebral AVMs, our group at Stanford University has used CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) to treat selected spinal cord AVMs since 1997. In this article, we retrospectively analyze our preliminary experience with this technique. Fifteen patients with intramedullary spinal cord AVMs (nine cervical, three thoracic, and three conus medullaris) were treated by image-guided SRS between 1997 and 2005. SRS was delivered in two to five sessions with an average marginal dose of 20.5 Gy. The biologically effective dose used in individual patients was escalated gradually over the course of this study. Clinical and magnetic resonance imaging follow-up were carried out annually, and spinal angiography was repeated at 3 years. After a mean follow-up period of 27.9 months (range, 3-59 mo), six of the seven patients who were more than 3 years from SRS had significant reductions in AVM volumes on interim magnetic resonance imaging examinations. In four of the five patients who underwent postoperative spinal angiography, persistent AVM was confirmed, albeit reduced in size. One patient demonstrated complete angiographic obliteration of a conus medullaris AVM 26 months after radiosurgery. There was no evidence of further hemorrhage after CyberKnife treatment or neurological deterioration attributable to SRS. This description of CyberKnife radiosurgical ablation demonstrates its feasibility and apparent safety for selected intramedullary spinal cord AVMs. Additional experience is necessary to ascertain the optimal radiosurgical dose and ultimate efficacy of this technique.