Training Cerebrovascular and Neuroendovascular Surgery Residents: A Systematic Literature Review and Recommendations.

Background: The rapid evolution of neuroendovascular intervention has resulted in the inclusion of endovascular techniques as a core competency in neurosurgical residency training. Methods: We conducted a literature review of studies involving the training of neurosurgical residents in cerebrovascular and endovascular neurosurgery. We reviewed the evolution of cerebrovascular neurosurgery and the effects of these changes on residency, and we propose interventions to supplement contemporary training. Results: A total of 48 studies were included for full review. Studies evaluated trainee education and competency (29.2%, 14/48), neuroendovascular training models (20.8%, 10/48), and open cerebrovascular training models (52.1%, 25/48), with some overlap. We used a qualitative analysis of reviewed reports to generate a series of suggested training supplements to optimize cerebrovascular education. Conclusion: Cerebrovascular neurosurgery is at a crossroads where trainees must develop disparate skill sets with inverse trends in volume. Continued longitudinal exposure to both endovascular and open cerebrovascular surgical fields should be mandated in general resident education, and blended learning tactics using adjunct simulation systems and models should be incorporated with didactics to both optimize learning and alleviate restraints placed by decreased volume and autonomy.

Diffusely invasive supratentorial rosette-forming glioneuronal tumor: illustrative case.

BACKGROUND: Rosette-forming glioneuronal tumors (RGNTs) are rare tumors composed of mixed glial and neurocytic components. Most lesions are confined to the posterior fossa, especially in the region of the fourth ventricle, in young adults. In few instances, diffuse involvement of the supratentorial region is identified, thereby creating significant challenges in diagnosis, surgical intervention, and prognostication. OBSERVATIONS: The authors present a 23-year-old female with chronic headaches, papilledema, and hydrocephalus who underwent radiographic evaluation revealing obstructive hydrocephalus and diffuse supratentorial enhancing and nonenhancing cystic and nodular lesions. The patient underwent a right frontal craniotomy and septostomy. An exophytic nonenhancing right frontal horn lesion was resected, and an enhancing third-ventricular lesion was biopsied. Final pathology of both of the lesions sampled was consistent with RGNT. Next-generation sequencing demonstrated tumor alterations in the FGFR-1 and PIK3CA genes. Targeted therapy with the FGFR inhibitor erdafitinib demonstrated a partial remission. LESSONS: Diffuse supratentorial spread of RGNT is an extremely rare presentation of an already uncommon pathology. In some cases, gross-total resection may not be feasible. Goals of surgery include acquiring tissue for diagnosis, maximizing safe resection, and treating any associated hydrocephalus. FGFR inhibitors may be of benefit in cases of disease progression.

The Longissimus Capitis Insertion as a Superficial Landmark for the Sigmoid Sinus: An Anatomical Study.

Objective Many external anatomical landmarks have been used for approximating deeper, intracranial structures. Herein, we evaluate the attachment of the longissimus capitis (LC) on the mastoid process as a landmark for the underlying sigmoid sinus. Methods Adult cadavers underwent dissection of the posterior occiput with special attention to the attachment of the LC muscle. Once the periphery of the muscle's tendon of attachment was determined, a burr hole was made in this area and evaluated internally for its relationship to the sigmoid sinus. Results From an intracranial view, burr holes on all sides were over the sigmoid sinus and just slightly lateral to the center of the sinus. The distance from the midline to the medial border of the insertion of the LC had a mean of 63.0 ± 7.2 mm. The width of the tendon of insertion of the LC on the mastoid process had a mean of 17.6 ± 5.7 mm. The length of the tendon insertion of the LC had a mean of 14.7 ± 4.7 mm. The distance from the inferior border of the insertion of the LC to the tip of the mastoid process had a mean of 6.2 ± 4.5 mm. Conclusion To our knowledge, use of the attachment site of the LC on the mastoid process as an external landmark for the underlying sigmoid sinus has not previously been reported. Based on our cadaveric findings, the sigmoid sinus is centered under the attachment of the LC regardless of the width of its tendon.

Detethering the superficial temporal artery: Application to tension free superficial temporal artery-middle cerebral artery bypasses.

Extracranial-intracranial bypass has been shown to be effective in the surgical treatment of moyamoya disease, complex aneurysms, and tumors that involve proximal vasculature in carefully selected patients. Branches of the superficial temporal artery (STA) are used commonly for the bypass surgery; however, an appropriate length of the donor vessel must be harvested to avoid failure secondary to anastomotic tension. The goal of this cadaveric study was to investigate quantitatively operative techniques that can increase the STA length available to facilitate tension-free STA-middle cerebral artery (MCA) bypass. We conducted a cadaveric study using a total of 16 sides in eight cadavers. Measurements of the STA trunk with its frontal branch (STAfb) were taken before and after skeletonization and detethering of the STA with the STAfb and mobilization of the parietal branch of the STA. A final measurement of the STA with the STAfb was taken for the free length gained toward visible proximal cortical branches of the MCA. Paired student's t-tests were used to compare the mean length before and after mobilization and unpaired t-tests to analyze according to laterality. The mean length of the STA with the STAfb was 9.0 cm prior to modification. After skeletonization and mobilization, the mean lengths increased significantly to 10.5 and 11.3 cm, respectively (p < 0.05). Especially in the cases that had the coiled and tortuous STA, skeletonization was considerably effective to increase the length of the STA with the STAfb. After simulating a bypass by bringing the STAfb to the recipient MCA site, the mean extended length of the STA with the STAfb was 3.0 cm. There were no statistically significant differences between sides in all measurements. We report a significant increase in the mean STA length available (3.0 cm) following skeletonization and mobilization. Clinical applications of the extended length of the STA with the STAfb may facilitate tension-free STA-MCA bypasses and improve outcomes. Further studies are needed in a clinical context.

Vertebral artery dissection and associated ruptured intracranial pseudoaneurysm successfully treated with coil assisted flow diversion: A case report and review of the literature.

Dissecting intracranial pseudoaneurysms (IPs) are associated with a high incidence of rupture and poor neurologic outcomes. Lesions in the posterior circulation are particularly malignant and pose even greater management challenges. Traditional management consists of microsurgical vessel sacrifice with or without bypass. Flow diversion (FD) in the setting of subarachnoid hemorrhage (SAH) represents a reconstructive treatment option and can be paired with coil embolization to promote more rapid thrombosis of the lesion. We report a case of a ruptured dissecting vertebral artery (VA) IP successfully acutely treated with coil-assisted FD. A 53-year-old male presented with a right V4 dissection spanning the origin of the posterior inferior cerebellar artery and associated ruptured V4 IP. The patient was treated with coil-assisted FD. Oral dual-antiplatelet therapy (DAPT) was initiated during the procedure, and intravenous tirofiban was used as a bridging agent. Immediate obliteration of the IP was achieved, with near-complete resolution of the dissection within 48 h. The patient made a complete recovery, and angiography at 6 weeks confirmed total IP obliteration, reconstruction of the VA, and a patent stent. The use of FD and DAPT in the setting of acute SAH remains controversial. We believe that coil-assisted FD in carefully selected patients offers significant advantages over traditional microsurgical and endovascular options. The risks posed by DAPT and potential for delayed thrombosis with FD can be effectively mitigated with planning and the development of protocols. We discuss the current literature in the context of our case and review the challenges associated with treating these often devastating lesions.

Middle Fossa Encephaloceles Treated via the Transmastoid Approach: A Case Series and Review of the Literature.

BACKGROUND: Middle fossa (MF) encephaloceles are rare lesions resulting from herniation through defects in the tegmen tympani or mastoideum. Underlying etiologies and clinical presentations are variable. Surgical goals include fistula obliteration, resection of nonfunctioning parenchyma, and dehiscence repair. The middle cranial fossa approach (MCFA), transmastoid approach (TMA), and combined (MCFA + TMA) approaches have been described. The minimally invasive TMA provides excellent exposure of the pathology and allows for ample working room to repair the defect. OBJECTIVE: To present short-term follow-up results in patients treated via the TM repair at our institution. METHODS: A retrospective review of patients with symptomatic encephaloceles treated via the TMA by our multidisciplinary team. Patient demographics, clinical presentations, intraoperative findings, repair technique, and outcomes were highlighted. RESULTS: A total of 16 encephaloceles in 13 patients were treated. Defect etiologies included spontaneous (50.0%), secondary to chronic infection (25.0%), or cholesteatoma (18.8%). Defects were most often within the tegmen mastoideum (68.8%). Average length of surgery was 3.3 h (95% CI: 2.86-3.67) and length of stay 3.9 d (95% CI: 3.09-4.79). On short-term follow-up (average 11.5 mo), no patients experienced postoperative cerebrospinal fluid leak or recurrence. The majority of patients (83.3%) experienced confirmed improvement or stabilization of hearing. CONCLUSION: MF encephaloceles present with various clinical manifestations and result from multiple underlying etiologies. The TMA is an alternative to craniotomy and our short-term results suggest that this approach may be utilized effectively in appropriately selected cases.

Iatrogenic Middle Cerebral Artery Ruptured Pseudoaneurysm Successfully Treated With a Pipeline Embolization Device.

Background: Endovascular advances have shifted the treatment algorithms for traumatic intracranial pseudoaneurysms (IPs) from vessel sacrifice to reconstruction. The Pipeline embolization device (PED) is a flow-diverting stent that promotes endothelialization across the lesion and reconstitutes the parent vessel lumen. Case Report: A 66-year-old male with a history of a right orbital apex lesion presented for biopsy with ophthalmology. Ophthalmology performed a right lateral orbitotomy complicated by brisk arterial bleeding from a proximal right middle cerebral artery (MCA) pseudoaneurysm. The MCA pseudoaneurysm was treated endovascularly with a PED, resulting in immediate stasis of contrast within the lesion without compilation. Interval follow-up angiograms 6 weeks and 6 months after the procedure showed no evidence of recurrence and a widely patent stent. Conclusion: The PED provided a rapid, minimally invasive, and durable treatment option for an acutely ruptured IP. We illustrate that endovascular management with flow diversion can be effectively used in select cases and provides a way to reconstruct the damaged vessel lumen and obliterate the aneurysm.

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

BACKGROUND: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion. METHODS: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches. RESULTS: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035). CONCLUSION: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

Treatment with dimethyl fumarate reduces the formation and rupture of intracranial aneurysms: Role of Nrf2 activation.

Oxidative stress and chronic inflammation in arterial walls have been implicated in intracranial aneurysm (IA) formation and rupture. Dimethyl fumarate (DMF) exhibits immunomodulatory properties, partly via activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway which reduces oxidative stress by inducing the antioxidant response element (ARE). This study evaluated the effects of DMF both in vitro, using tumor necrosis factor (TNF)-α-treated vascular smooth muscle cells (VSMC), and in vivo, using a murine elastase model to induce aneurysm formation. The mice were treated with either DMF at 100 mg/kg/day P.O. or vehicle for two weeks. DMF treatment protected VSMCs from TNF-α-induced inflammation as demonstrated by its downregulation of cytokines and upregulation of Nrf2 and smooth muscle cell markers. At higher doses, DMF also inhibited the pro-proliferative action of TNF-α by increasing apoptosis which protected the cells from aponecrosis. In mice, DMF treatment significantly decreased the incidence of aneurysm formation and rupture, at the same time increasing Nrf2 levels. DMF demonstrated a neuroprotective effect in mice with a resultant inhibition of oxidative stress, inflammation, and fibrosis in the cerebrovasculature. This suggests a potential role for DMF as a rescue therapy for patients at risk for formation and rupture of IAs.

Cauda Equina Syndrome Secondary to Diffuse Infiltration of the Cauda Equina by Acute Myeloid Leukemia: Case Report and Literature Review.

BACKGROUND: Cauda equina syndrome (CES) results from the dysfunction of the lumbar, sacral, and coccygeal rootlets composing the cauda equina. The underlying etiology is most commonly compression secondary to a large herniated lumbosacral disk; however, any pathology affecting the rootlets can result in the syndrome. METHODS: We present a rare case of CES secondary to neoplastic polyradiculitis in a patient with acute myelogenous leukemia (AML) and review the pertinent literature. A 72-year-old male with a medical history of AML presented with 2 weeks of difficulty ambulating, followed by acute-onset low back pain radiating to the buttocks bilaterally. RESULTS: Imaging of the lumbar spine demonstrated diffuse enhancement and thickening of the cauda equina rootlets. Lumbar puncture showed numerous blasts with monocytoid features consistent with AML, and the patient was diagnosed with polyradiculopathy of the cauda equina secondary to diffuse metastatic infiltration. CONCLUSIONS: Central nervous system involvement of leukemia is poorly understood, even though such lesions are not uncommon in advanced disease. As treatment has improved, many types of leukemia, such as AML, are believed to be curable, and patients with the disease are living longer. With improved survival, it is reasonable to suspect that such involvement by AML may become more common. Our patient is a classic presentation of CES secondary to diffuse infiltration by AML and serves as an example of this rare manifestation of hematologic malignancy.

Surgical Approaches in the Treatment of Intracranial Complications of Paranasal Sinus Disease: A Review of the Literature.

BACKGROUND: Intracranial extension of frontal or ethmoid sinusitis carries a high morbidity and mortality if not treated aggressively. With the emergence of endoscopic sinus surgery (ESS), we questioned whether these approaches have supplanted traditional transcranial procedures for intracranial extension of sinus disease, and whether ESS approaches had a difference in patient outcomes. METHODS: Studies reporting surgical management and outcomes of frontal sinus disease with intracranial extension were queried using the United States National Library of Medicine at the National Institutes of Health PubMed database. We also queried common internet search engines. We included studies regarding sinogenic intracranial suppurative infections treated surgically with ESS and neurosurgical approaches. Studies with insufficient data regarding specific treatment methods and studies that included populations of medically treated infections were excluded. RESULTS: A total of 108 cases were identified in which patients with intracranial sinogenic disease were treated via ESS alone (morbidity: 43.5%, mortality: 0.9%), 47 cases via transcranial intervention alone (morbidity: 33.2%, mortality: 7.8%), and 43 cases via simultaneous neurosurgical and ESS approaches (morbidity: 16.3%, mortality: 6.4%). Complex sinus disease with posterior table compromise in the absence of intracranial extension treated via ESS alone was reported in 164 cases with a morbidity and mortality of 3.8% and 0%, respectively. CONCLUSIONS: Combined ESS and transcranial approaches achieve definitive control of sinogenic and intracranial disease, whereas either modality alone carries a potential risk for higher morbidity and mortality. The use of ESS alone may have use in the treatment of sinusitis with posterior table erosion prior to intracranial extension.

Characterization of Glycolytic Enzymes and Pyruvate Kinase M2 in Type 1 and 2 Diabetic Nephropathy.

OBJECTIVE: Elevated glycolytic enzymes in renal glomeruli correlated with preservation of renal function in the Medalist Study, individuals with ≥50 years of type 1 diabetes. Specifically, pyruvate kinase M2 (PKM2) activation protected insulin-deficient diabetic mice from hyperglycemia-induced glomerular pathology. This study aims to extend these findings in a separate cohort of individuals with type 1 and type 2 diabetes and discover new circulatory biomarkers for renal protection through proteomics and metabolomics of Medalists' plasma. We hypothesize that increased glycolytic flux and improved mitochondrial biogenesis will halt the progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: Immunoblots analyzed selected glycolytic and mitochondrial enzymes in postmortem glomeruli of non-Medalists with type 1 diabetes (n = 15), type 2 diabetes (n = 19), and no diabetes (n = 5). Plasma proteomic (SOMAscan) (n = 180) and metabolomic screens (n = 214) of Medalists with and without stage 3b chronic kidney disease (CKD) were conducted and significant markers validated by ELISA. RESULTS: Glycolytic (PKM1, PKM2, and ENO1) and mitochondrial (MTCO2) enzymes were significantly elevated in glomeruli of CKD- versus CKD+ individuals with type 2 diabetes. Medalists' plasma PKM2 correlated with estimated glomerular filtration rate (r 2 = 0.077; P = 0.0002). Several glucose and mitochondrial enzymes in circulation were upregulated with corresponding downregulation of toxic metabolites in CKD-protected Medalists. Amyloid precursor protein was also significantly upregulated, tumor necrosis factor receptors downregulated, and both confirmed by ELISA. CONCLUSIONS: Elevation of enzymes involved in the metabolism of intracellular free glucose and its metabolites in renal glomeruli is connected to preserving kidney function in both type 1 and type 2 diabetes. The renal profile of elevated glycolytic enzymes and reduced toxic glucose metabolites is reflected in the circulation, supporting their use as biomarkers for endogenous renal protective factors in people with diabetes.

Acute Presentation of Vestibular Schwannoma Secondary to Intratumoral Hemorrhage: A Case Report and Literature Review.

BACKGROUND: Vestibular schwannomas (VS) are common slow-growing tumors that typically present with the insidious progression of unilateral hearing loss, tinnitus, vertigo, and gait imbalance. Clinically significant intratumoral acute hemorrhage is exceedingly rare and can present with the acute onset of symptoms, neurologic deterioration, and significant dysfunction of cranial nerves VII and VIII. We discuss a 40-year-old man who developed mild hearing loss and headaches over the course of a month before presenting with a large acutely hemorrhagic vestibular schwannoma. In addition, we review the current literature pertaining to this pathology. CASE PRESENTATION: A previously healthy 40-year-old man with a 1-month history of mild headaches, dizziness, and left-sided hearing loss, tinnitus, and facial numbness presented with the acute onset of severe headache, vomiting, complete left-sided hearing loss, and left-sided facial weakness. Computed tomography and magnetic resonance imaging revealed a 4.1 × 2.7 cm hemorrhagic mass in the left cerebellopontine angle most consistent with VS. The patient subsequently underwent a retrosigmoid craniotomy and resection of the tumor. Pathology was consistent with hemorrhagic VS. Imaging at 1-year follow-up demonstrated no residual or recurrent disease, and facial motor function had completely recovered. CONCLUSIONS: Histologically, vascular abnormalities and microhemorrhages are nearly ubiquitous across vestibular schwannomas and may contribute to cystic degeneration and rapid tumor growth. However, clinically significant hemorrhage is rarely encountered and is more commonly associated with more profound neurologic sequelae and cranial nerve VII dysfunction. Surgical resection at the time of presentation should be strongly considered to remove the risk of repeat hemorrhage and further deterioration. Our case represents a typical presentation and clinical course for a patient presenting with this rarely encountered pathology.

Lymphoma of the Optic Apparatus in an Immunocompetent Patient: A Case Report and Review of the Literature.

BACKGROUND: Primary optic apparatus involvement by lymphoma is an exceedingly rare entity, with only 3 cases previously reported in the literature. Whether this represents a distinct pathology, metastatic disease from an unidentified systemic lymphoma, or the first manifestation of evolving primary central nervous system lymphoma is not currently understood. CASE DESCRIPTION: We present a case of a young immunocompetent male with rapidly progressive visual loss who was found to have isolated lymphomatous involvement of the optic apparatus. We discuss the classification of the lesion, the clinical presentation, the diagnostic workup, and the visual and overall prognosis. Special consideration is given to the operative approach and selecting an appropriate site for biopsy based on the visual exam at the time of presentation. CONCLUSIONS: Primary optic nerve lymphoma is a rare disease that requires a systemic workup and a multidisciplinary approach to treatment.

Pipeline Embolization Device for the Treatment of Intracranial Pseudoaneurysms.

BACKGROUND: Intracranial pseudoaneurysms (PSAs) are associated with high rupture and mortality rates and have traditionally been treated by parent vessel sacrifice. There has been recent interest in using flow-diverting devices for treatment of these complex lesions while preserving flow through the parent artery. The objective of this study is to examine the safety and efficacy of these devices in the treatment of intracranial PSA. METHODS: We performed a multi-institutional retrospective study of intracranial PSAs treated with the Pipeline Embolization Device (PED) between 2014 and 2017 at 7 institutions. Complications and clinical and radiographic outcomes were reviewed. RESULTS: A total of 19 patients underwent PED placement for intracranial PSA. Iatrogenic injury and trauma comprised most etiologies in our series. The mean pseudoaneurysm diameter was 8.8 mm, and 18 of 19 PSAs (95%) involved the internal carotid artery (ICA). Multiple PEDs were deployed in a telescoping fashion in 7 patients (37%). Of the 18 patients with follow up imaging, 14 (78%) achieved complete pseudoaneurysm obliteration and 2 achieved near-complete obliteration (11%). Two patients (11%) were found to have significant pseudoaneurysm progression on short-term follow-up and required ICA sacrifice. No patients experienced new neurologic deficits or deterioration secondary to PED placement. No patients experienced bleeding or rebleeding from PSA. CONCLUSIONS: In well-selected patients, the use of flow-diverting stents may be a feasible alternative to parent vessel sacrifice. Given the high morbidity and mortality associated with PSA, we recommend short- and long-term radiographic follow-up for patients treated with flow-diverting stents.

miR-206 as a Biomarker for Response to Mesalamine Treatment in Ulcerative Colitis.

Background: MicroRNAs (miRNAs) are important post-translational regulators. Elevated levels of miR-206 in ulcerative colitis (UC) were associated with suppression of anti-inflammatory A3 adenosine receptor (A3AR) expression. However, the relationship of miR-206 to histologic remission in UC patients remains unknown. This study correlates expression levels of miR-206 with histologic remission in patients treated via long-term mesalamine treatment to identify a possible mode of action for this mainstay drug for UC. Methods: Expression of miR-206 and its target A3AR were analyzed in HT29 cell line before and after mesalamine treatment (2 mM) at different time points (0, 4, 12, and 24 hours) by qRT-PCR and western blot analysis. Expression of miR-206 and pathological scores of colonoscopic biopsy specimens were studied in 10 UC patients treated with mesalamine treatment for 2 to 6 years. Results: miR-206 transcripts decreased 2.23-fold (P = 0.0001) 4 hours after 2 mM mesalamine treatment in HT29 colon cells compared with untreated controls. However, the mRNA/protein levels of A3AR increased by 4-fold (P = 0.04) and 2-fold, respectively, in same cells. miR-206 relative expression decreased significantly in patients treated with 4.8 g of mesalamine (P = 0.002) but not with 2.4 g (P = 0.35). Tissue assessment of sequential mesalamine-treated colonoscopic biopsies indicate a strong correlation between downregulation of miR-206 and histologic improvement (R = 0.9111). Conclusion: Mesalamine treatment has an effect on epithelial miRNAs. Downregulation of miR-206 by long-term mesalamine treatment may confer a protective effect in inducing and maintaining histologic remission. Thus, miR-206 expression levels can be utilized as a possible biomarker for therapeutic response to mesalamine treatment.

Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis.

BACKGROUND: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. AIM: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. METHODS: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2-6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. RESULTS: The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005-0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. CONCLUSION: This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.

Endovascular Management of Multiple Dysplastic Aneurysms in a Young Man with an Unknown Underlying Cause: A Case Report and Review of the Literature.

BACKGROUND: Intracranial aneurysms are the leading cause of nontraumatic subarachnoid hemorrhage and are most commonly associated with the anterior cerebral artery (ACA) and anterior communicating artery complex. We describe the presentation and management of a 27-year-old man with concurrent bilateral A1-2 junction aneurysms and fusiform intraorbital ophthalmic artery (OA) aneurysms. CASE DESCRIPTION: A 27-year-old man with no past medical history presented with 3 months of headaches. Imaging showed a large dysplastic left A1-2 junction aneurysm and a smaller saccular right A1-2 junction aneurysm, with potentially adherent domes. Two fusiform aneurysms of the intraorbital segment of the left OA were also identified. The patient underwent coil-assisted pipeline embolization of the left A1-A2 aneurysm, with complete obliteration and reconstitution of the normal parent vessel. The patient underwent coil embolization of the right A1-2 aneurysm 3 weeks later, which was found to have grown significantly at the time of treatment. Three-month follow-up showed spontaneous resolution of the OA aneurysms, persistent obliteration of the left aneurysm, and significant recurrence of the right aneurysm, which was treated with stent-assisted coil embolization. A second recurrence 3 months later was successfully treated with repeat coiling. At the time of this treatment, the patient was also found to have 2 de novo distal middle cerebral artery and ACA dysplastic aneurysms, which were not treated. Follow-up angiography 6 weeks later showed stable complete obliteration of the right A1-2 aneurysm and interval complete resolution of the dysplastic middle cerebral artery aneurysm. The distal ACA aneurysm was observed to have minimally increased in size; however, the parent vessel showed signs of interval partial thrombosis with contrast stasis within the aneurysm. This final aneurysm is being followed with serial imaging. The patient remains neurologically intact with complete resolution of his headaches. CONCLUSIONS: We report the case of a young man with no past medical history who presented with multiple dysplastic aneurysms. Successful staged endovascular intervention resulted in obliteration of aneurysms with spontaneous obliteration of the intraorbital OA aneurysms observed at 3 months. We present this case to review the multiple challenges of managing complex ACA aneurysms and to highlight the usefulness of endovascular intervention in their treatment.

Inflammatory mediators in vascular disease: identifying promising targets for intracranial aneurysm research.

Inflammatory processes are implicated in many diseases of the vasculature and have been shown to play a key role in the formation of intracranial aneurysms (IAs). Although the specific mechanisms underlying these processes have been thoroughly investigated in related pathologies, such as atherosclerosis, there remains a paucity of information regarding the immunopathology of IA. Cells such as macrophages and lymphocytes and their effector molecules have been suggested to be players in IA, but their specific interactions and the role of other components of the inflammatory response have yet to be determined. Drawing parallels between the pathogenesis of IA and other vascular disorders could provide a roadmap for developing a mechanistic understanding of the immunopathology of IA and uncovering useful targets for therapeutic intervention. Future research should address the presence and function of leukocyte subsets, mechanisms of leukocyte recruitment and activation, and the role of damage-associated molecular patterns in IA.