Lumbar stenosis due to wild-type transthyretin amyloid-induced thickening of the ligamentum flavum: a separate etiology from degeneration of intervertebral discs?

OBJECTIVE: Wild-type transthyretin amyloid (ATTRwt) is deposited in the ligamentum flavum (LF) of a subset of patients with spinal stenosis who undergo decompressive surgery, although its role in the pathophysiology of spinal stenosis is unknown. It has been theorized that degeneration of intervertebral discs causes increased mechanical stress and inflammatory/degenerative cascades and ultimately leads to LF fibrosis. If ATTRwt deposits contribute to LF thickening and spinal stenosis through a different pathway, then patients with ATTRwt may have less severe disc degeneration than those without it. In this study, the authors compared the severity of disc degeneration between patients with lumbar stenosis with and without amyloid in their LF to test whether ATTRwt is a unique contributor to LF thickening and spinal stenosis. METHODS: Of 324 consecutive patients between 2018 and 2019 who underwent decompression surgery for spinal stenosis and had LF samples sent for pathological analysis, 31 harboring ATTRwt were compared with 88 controls. Patient medical records were retrospectively reviewed for demographic and surgical information. Disc degeneration was assessed on preoperative T2-weighted MR images with the modified Pfirrmann grading system at every lumbar disc level. RESULTS: Baseline characteristics were similar between the groups, except for a statistically significant increase in age in the ATTRwt group. The crude unadjusted comparisons between the groups trended toward a less severe disc degeneration in the ATTRwt group, although this difference was not statistically significant. A multivariable linear mixed-effects model was created to adjust for the effects of age and to isolate the influence of ATTRwt, the presence of an operation at the level, and the specific disc level (between L1 and S1). This model revealed that ATTRwt, the presence of an operation, and the specific level each had significant effects on modified Pfirrmann scores. CONCLUSIONS: Less severe disc degeneration was noted in patients with degenerative spinal stenosis harboring ATTRwt compared with those without amyloid. This finding suggests that ATTRwt deposition may play a separate role in LF thickening from that played by disc degeneration. Future studies should aim to elucidate this potentially novel pathophysiological pathway, which may uncover an exciting potential for the development of amyloid-targeted therapies that may help slow the development of spinal stenosis.

The Relationship Between Wild-Type Transthyretin Amyloid Load and Ligamentum Flavum Thickness in Lumbar Stenosis Patients.

BACKGROUND: One key contributor to lumbar stenosis is thickening of the ligamentum flavum (LF), a process still poorly understood. Wild-type transthyretin amyloid (ATTRwt) has been found in the LF of patients undergoing decompression surgery, suggesting that amyloid may play a role. However, it is unclear whether within patients harboring ATTRwt, the amount of amyloid is associated with LF thickness. METHODS: From an initial cohort of 324 consecutive lumbar stenosis patients whose LF specimens from decompression surgery were sent for analysis (2018-2019), 33 patients met the following criteria: 1) Congo red-positive amyloid in the LF, 2) ATTRwt by mass spectrometry-based proteomics, and 3) an available preoperative magnetic resonance imaging. Histological specimens were digitized, and amyloid load was quantified through Trainable Weka Segmentation machine learning. LF thicknesses were manually measured on axial T2-weighted preoperative magnetic resonance imaging scans at each lumbar level, L1-S1. The sum of thicknesses at every lumbar LF level (L1-S1) equals "lumbar LF burden". RESULTS: Patients had a mean age of 72.7 years (range = 59-87), were mostly male (61%) and white (82%), and predominantly had surgery at L4-L5 levels (73%). Amyloid load was positively correlated with LF thickness (R = 0.345, P = 0.0492) at the levels of surgical decompression. Furthermore, amyloid load was positively correlated with lumbar LF burden (R = 0.383, P = 0.0279). CONCLUSIONS: Amyloid load is positively correlated with LF thickness and lumbar LF burden across all lumbar levels, in a dose-dependent manner. Further studies are needed to validate these findings, uncover the underlying pathophysiology, and pave the way toward using therapies that slow LF thickening.

Machine Learning Quantification of Amyloid Deposits in Histological Images of Ligamentum Flavum.

Wild-type transthyretin amyloidosis (ATTRwt) is an underdiagnosed and potentially fatal disease. Interestingly, ATTRwt deposits have been found to deposit in the ligamentum flavum (LF) of patients with lumbar spinal stenosis before the development of systemic and cardiac amyloidosis. In order to study this phenomenon and its possible relationship with LF thickening and systemic amyloidosis, a precise method of quantifying amyloid deposits in histological slides of LF is critical. However, such a method is currently unavailable. Here, we present a machine learning quantification method with Trainable Weka Segmentation (TWS) to assess amyloid deposition in histological slides of LF. Images of ligamentum flavum specimens stained with Congo red are obtained from spinal stenosis patients undergoing laminectomies and confirmed to be positive for ATTRwt. Amyloid deposits in these specimens are classified and quantified by TWS through training the algorithm via user-directed annotations on images of LF. TWS can also be automated through exposure to a set of training images with user-directed annotations, and then applied] to a set of new images without additional annotations. Additional methods of color thresholding and manual segmentation are also used on these images for comparison to TWS. We develop the use of TWS in images of LF and demonstrate its potential for automated quantification. TWS is strongly correlated with manual segmentation in the training set of images with user-directed annotations (R = 0.98; p = 0.0033) as well as in the application set of images where TWS was automated (R = 0.94; p = 0.016). Color thresholding was weakly correlated with manual segmentation in the training set of images (R = 0.78; p = 0.12) and in the application set of images (R = 0.65; p = 0.23). TWS machine learning closely correlates with the gold-standard comparator of manual segmentation and outperforms the color thresholding method. This novel machine learning method to quantify amyloid deposition in histological slides of ligamentum flavum is a precise, objective, accessible, high throughput, and powerful tool that will hopefully pave the way towards future research and clinical applications.

Metal allergy hypersensitivity after posterior thoracic spinal fusion: A case report and review of the literature.

Background: Spine surgeons rarely consider metal allergies when placing hardware, as implants are thought to be inert. Case Description: A 32-year-old male presented with a skin rash attributed to the trace metal in his spinal fusion instrumentation. Patch testing revealed sensitivities to cobalt, manganese, and chromium. He underwent hardware removal and replacement with constructs of commercially pure titanium. His skin findings resolved at 2 weeks after surgery and were stable at 6 weeks. Conclusion: Hypersensitivity to metal (i.e., metal allergy) should be considered before performing instrumented spinal fusions.

Abdominal Fat Graft for Sellar Reconstruction: Retrospective Outcomes Review and Technical Note.

BACKGROUND: The transsphenoidal approach is the standard of care for the treatment of pituitary adenomas and is increasingly employed for many anterior skull base tumors. Persistent postoperative cerebrospinal fluid (CSF) leaks can result in significant complications. OBJECTIVE: To analyze our series of patients undergoing abdominal fat graft repair of the sellar floor defect following transsphenoidal surgery, describe and investigate our current, routine technique, and review contemporary and past methods of skull base repair. METHODS: A recent consecutive series (2008-2017) of 865 patients who underwent 948 endonasal procedures for lesions of the sella and anterior skull base was retrospectively reviewed. Three hundred eighty patients underwent reconstruction of the sellar defect with an abdominal fat graft. RESULTS: The diagnoses of the 380 patients receiving fat grafts were the following: 275 pituitary adenomas (72.4%), 50 Rathke cleft cysts (13.2%), 12 craniopharyngiomas (3.2%), and a variety of other sellar lesions. Fourteen patients had persistent postoperative CSF leak requiring reoperation and included: 5 pituitary adenomas (1.3%), 4 craniopharyngiomas (1.1%), 2 arachnoid cysts (0.53%), 2 prior CSF leaks (0.53%), and 1 Rathke cleft cyst (0.26%). Four patients (1.1%) developed minor abdominal donor site complications requiring reoperation: 1 hematoma, 2 wound complications, and 1 keloid formation resulting in secondary periumbilical infection. CONCLUSION: Minimizing postoperative CSF leaks following endonasal anterior skull base surgery is important to decrease morbidity and to avoid a prolonged hospital stay. We present an evolved technique of abdominal fat grafting that is effective and safe and includes minimal morbidity and expense.

A modern series of subdiaphragmatic craniopharyngiomas.

OBJECTIVE: The endoscopic endonasal approach has been proposed as a primary surgical strategy for select craniopharyngiomas. However, those tumors that arise from the sella have not been classified with the other craniopharyngioma subtypes in terms of surgical nuances, intraoperative findings, and postoperative outcomes. The authors describe their experience with a select subtype of craniopharyngioma arising within the sella subjacent to the diaphragma sellae and refer to these tumors as type 0. METHODS: After obtaining IRB approval, three institutions retrospectively reviewed their data collected from 2005 to 2017. Patients eligible for inclusion in the study were those who had tumors that originated from the sella inferior to the diaphragma sellae. Demographic, clinical, radiological, surgical, and follow-up data were examined and analyzed. RESULTS: Twenty-eight patients (average age 19.3 years, range 3-60 years) were included in this study. Sixteen patients (57%) were younger than 18 years of age. All patients had characteristic imaging features of an expanded sella. Seventy-five percent of the patients presented with some form of visual field deficit (89% had radiographic optic apparatus compression) and 39% with hypopituitarism. The average maximal tumor diameter in the axial, coronal, or sagittal plane was 3.1 cm. Gross-total resection was achieved in 82% of the patients. Twenty-one percent of patients experienced an iatrogenic complication, and there were only two cases (7%) of postoperative cerebrospinal fluid (CSF) leakage. Only two patients (7%) required the use of a nasoseptal flap as part of their original reconstruction. Pathology was uniformly the adamantinomatous subtype. Postoperative objective visual outcomes were improved in 71% of the patients with visual symptoms or visual field deficits on presentation and stable in 24%. Mean follow-up was 45.1 months (range 3-120 months) with an 18% recurrence rate at a mean of 44.4 months (range 10-84 months). One patient was lost to follow-up. Thirty-six percent of patients received postoperative radiation to treat recurrence or residual tumor. Endocrine data are also presented. CONCLUSIONS: Craniopharyngiomas that originate within the sella below the diaphragma sellae are a select subtype characterized by 1) an enlarged sella, 2) an intact diaphragma sellae at surgery, and 3) an adamantinomatous pathology. These tumors can be treated transnasally without the absolute need for neurovascular flap reconstruction, as there is a low risk of CSF leakage.

Demonstration of Infectious Transgression Through the Skull Base Occurring 9 Years After Pituitary Adenoma Resection.

BACKGROUND: Sellar infections represent less than 1% of all sellar lesions and can be life-threatening. These infections occur de novo in up to 70% of patients or can less commonly develop after surgical treatment of another primary lesion, such as a pituitary adenoma. CASE DESCRIPTION: We report a unique case of a 27-year-old woman with a recurrent pituitary adenoma treated with 2 previous transsphenoidal resections. She ultimately presented with hypopituitarism, followed by headaches, malaise, chills, and visual-field and acuity deficits 9 years after her second transsphenoidal resection. During the second operation, the sellar floor was reconstructed with hydroxyapatite bone cement. On the most recent presentation, magnetic resonance imaging of the brain and pituitary demonstrated a residual sellar mass accompanied by significant enhancement and T2 hyperintensity of the infundibulum, hypothalamus, optic chiasm, and optic tracts. The patient was started on empiric antibiotics and steroids before frank purulence in the sella was discovered and removed by transsphenoidal endoscopy. Cultures were positive for methicillin-sensitive Staphylococcus aureus and Propionibacterium acnes. At her 3-month follow-up evaluation, the patient had complete resolution of her symptoms and radiographic findings. CONCLUSIONS: This case demonstrates the fact that patients with pituitary lesions who have foreign material used for surgical closure can present with infections many years after the initial intervention. Furthermore, with appropriate clinical diagnosis and treatment, the reactive inflammation caused by sellar infection is reversible. We review the literature regarding the risk factors and management strategies for delayed postoperative sellar infections.

Flow Diverter Therapy With the Pipeline Embolization Device Is Associated With an Elevated Rate of Delayed Fluid-Attenuated Inversion Recovery Lesions.

BACKGROUND AND PURPOSE: Flow diversion using the Pipeline Embolization Device is reported as a safe treatment of aneurysms. Complete aneurysm occlusion, however, occurs in a delayed fashion with initial persistent filling of the aneurysm dome. We hypothesized that this transflow across metallic struts may be associated with thromboembolic events. METHODS: Forty-one consecutive patients undergoing aneurysm treatment with the Pipeline Embolization Device and a comparison group of 78 Neuroform stent-mediated embolizations were studied. Patients' charts, procedure notes, platelet function, and anticoagulation state were analyzed. Serial magnetic resonance images were assessed for the presence of newly occurring diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) lesions at multiple postprocedure time ranges (average days post procedure [Pipeline Embolization Device/Neuroform]: T1=1, T2=73/107, T3=174, T4=277/335, and T5=409). In addition, diffusion-weighted imaging or FLAIR burden was estimated by lesional diameter summation. RESULTS: Pipeline patients were more likely to have new ipsilateral FLAIR lesions at all time points studied (30.6% versus 7.2% of patients at T=2 and 34.5% versus 6.2% at T=4). The mean FLAIR burden was significantly increased for Pipeline patients (10.1 versus 0.7 mm at T=2 and 8.8 versus 1.9 mm at T=4). Overall 34% (14/41) of Pipeline patients experienced a new FLAIR lesion at anytime when compared with 10% (8/78) of Neuroform stent-coil patients. Postprocedural diffusion-weighted imaging did not predict future FLAIR lesions suggesting a nonprocedural cause. CONCLUSIONS: The Pipeline Embolization Device is associated with increased rate of de novo FLAIR lesions occurring in a delayed fashion and distinct from perioperative diffusion-weighted imaging lesions. The cause and clinical effect of these lesions are unknown and suggest the need for prudent follow-up and evaluation.

Iatrogenic Spinal Cord Injury during Removal of the Inferior Articular Process in the Presence of Ossification of the Ligamentum Flavum.

Ossified ligamentum flavum (OLF) is a condition of heterotopic lamellar bone formation within the yellow ligament. Some patients with OLF can be asymptomatic. However, asymptomatic OLF may not be obvious on preoperative MRI and could increase the risk of iatrogenic injury during treatments for unrelated spinal conditions. This report describes a case of spinal cord injury caused by the indirect transmission of force from an osteotome to an asymptomatic OLF during the resection of a thoracic inferior articular process (IAP). To prevent this outcome, we urge careful review of CT imaging in the preoperative setting and advocate the use of a high-speed drill instead of an osteotome during bone removal in the setting of an adjacent area of OLF.

Early Identification of Traumatic Durotomy Associated with Atlantooccipital Dislocation May Prevent Retropharyngeal Pseudomeningocele Development.

Atlantooccipital dislocation can be complicated by a traumatic durotomy that may lead to the rare development of a retropharyngeal pseudomeningocele. To our knowledge this has been reported only five times previously. We present the case of a 60-year-old man involved in a motor vehicle accident who suffered an atlantooccipital dislocation and C5-C6 three-column injury. A unique MRI image of a defect in the ventral dura posterior to C2 was appreciated. He underwent occiput to T2 internal fixation and arthrodesis. During surgery, CSF egress was seen caudal to the right C2 nerve root. A DuraMatrix onlay patch reinforced with DuraSeal was placed to stop the CSF leak. A lumbar subarachnoid drain was also placed. The patient made a satisfactory recovery with residual mild weakness of his right upper extremity. In this report, we demonstrate that careful MRI review can reveal a ventral durotomy in a traumatic atlantooccipital dislocation and, if discovered, effective treatment including a lumbar subarachnoid drain for CSF diversion may prevent progression to a retropharyngeal pseudomeningocele. The literature on this rare presentation and associated durotomy is provided.

The effect of spinal osteotomies on spinal cord tension and dural buckling: a cadaveric study.

OBJECT: The standard surgical release of a tethered cord may result in recurrent scar formation and occasionally be associated with retethering. The application of spinal shortening procedures to this challenging problem potentially can reduce tension on the retethered spinal cord while minimizing the difficulties inherent in traditional lumbosacral detethering revision. Although spinal shortening procedures have proven clinical benefit in patients with a recurrent tethered cord, it is unclear how much shortening is required to achieve adequate reduction in spinal cord tension or what impact these osteotomies have on dural buckling. METHODS: The authors calculated mean values from 4 human cadavers to evaluate the effect of 3 different spinal shortening procedures--Smith-Petersen osteotomy (SPO), pedicle subtraction osteotomy (PSO), and vertebral column resection (VCR)--on spinal cord tension and dural buckling. Three cadavers were dedicated to the measurement of spinal cord tension, and 3 other cadavers were devoted to myelography to measure dural buckling parameters. RESULTS: The SPO was associated with a maximal decrease in spinal cord tension of 16.1% from baseline and no dural buckling with any degree of closure. The PSO led to a mean maximal decrease in spinal cord tension of 63.1% from baseline at 12 mm of closure and demonstrated a direct linear relationship between dural buckling and increasing osteotomy closure. Finally, VCR closure correlated with a mean maximal decrease in spinal cord tension of 87.2% from baseline at 10 mm of closure and also showed a direct linear relationship between dural buckling and increases in osteotomy closure. CONCLUSIONS: In this cadaveric experiment, the SPO did not lead to appreciable tension reduction, while a substantial response was seen with both the PSO and VCR. The rate of tension reduction may be steeper for the VCR than the PSO. Adequate tension relief while minimizing dural buckling may be optimal with 12-16 mm of posterior osteotomy closure based on this cadaveric experiment.

A novel classification system of lumbar disc degeneration.

The Pfirrmann and modified Pfirrmann grading systems are currently used to classify lumbar disc degeneration. These systems, however, do not incorporate variables that have been associated with lumbar disc degeneration, including Modic changes, a high intensity zone, and a significant reduction in disc height. A system that incorporates these variables that is easy to apply may be useful for research and clinical purposes. A grading system was developed that incorporates disc structure and brightness, presence or absence of Modic changes, presence or absence of a high intensity zone, and reduction in disc height (disc height less than 5mm). MRI of 300 lumbar discs in 60 patients were analyzed twice by two neurosurgeons. Intra and inter-observer reliabilities were assessed by calculating Cohen's κ values. There were 156 grade zero ("normal"), 50 grade one, 57 grade two, 26 grade three, 10 grade four, and one grade five ("worst") discs. Inter-observer reliability was substantial (κ = 0.66 to 0.77) for disc brightness/structure, Modic changes, and disc height. Inter-observer reliability was moderate (κ = 0.41) for high intensity zone. Intra-observer reliability was moderate to excellent (κ = 0.53 to 0.94) in all categories. Agreement on the total grade between reviewers occurred 71% of the time and a difference of one grade occurred in an additional 25% of cases. Lumbar disc degeneration can be graded reliably by this novel system. The advantage of this system is that it incorporates disc brightness/structure, Modic changes, high intensity zone, and a rigid definition of loss of disc height. This system might be useful in research studies evaluating disc degeneration. Further studies are required to demonstrate possible clinical utility in predicting outcomes after spinal treatments such as fusion.

Management of spinal cord injury-related scoliosis using pedicle screw-only constructs.

OBJECT: Almost all pediatric patients who incur a spinal cord injury (SCI) will develop scoliosis, and younger patients are at highest risk for curve progression requiring surgical intervention. Although the use of pedicle screws is increasing in popularity, their impact on SCI-related scoliosis has not been described. The authors retrospectively reviewed the radiographic outcomes of pedicle screw-only constructs in all patients who had undergone SCI-related scoliosis correction at a single institution. METHODS: Medical records and radiographs from Shriner's Hospital for Children-Philadelphia for the period between November 2004 and February 2011 were retrospectively reviewed. RESULTS: Thirty-seven patients, whose mean age at the index surgery was 14.91±3.29 years, were identified. The cohort had a mean follow-up of 33.2±22.8 months. The mean preoperative coronal Cobb angle was 65.5°±25.7°, which corrected to 20.3°±14.4°, translating into a 69% correction (p<0.05). The preoperative coronal balance was 24.4±22.6 mm, with a postoperative measurement of 21.6±20.7 mm (p=1.00). Preoperative pelvic obliquity was 12.7°±8.7°, which corrected to 4.1°±3.8°, translating into a 68% correction (p<0.05). Preoperative shoulder balance, as measured by the clavicle angle, was 8.2°±8.4°, which corrected to 2.7°±3.1° (67% correction, p<0.05). Preoperatively, thoracic kyphosis measured 44.2°±23.7° and was 33.8°±11.5° postoperatively. Thoracolumbar kyphosis was 18.7°±12.1° preoperatively, reduced to 8.1°±7.7° postoperatively, and measured 26.8°±20.2° at the last follow-up (p<0.05). Preoperatively, lumbar lordosis was 35.3°±22.0°, which remained stable at 35.6°±15.0° postoperatively. CONCLUSIONS: Pedicle screw constructs appear to provide better correction of coronal parameters than historically reported and provide significant improvement of sagittal kyphosis as well. Although pedicle screws appear to provide good radiographic results, correlation with clinical outcomes is necessary to determine the true impact of pedicle screw constructs on SCI-related scoliosis correction.

Delayed progressive bilateral supraclinoid internal carotid artery stenosis in a patient with a ruptured basilar artery aneurysm.

Cerebral vasospasm is a common radiographic and clinical diagnosis after subarachnoid hemorrhage. Conventional treatments include medical hypertension, hypervolemia, and modest hemodilution. When medical treatments fail in severe vasospasm cases, intra-arterial vasodilation and balloon angioplasty may be useful. We present a 47-year-old woman with a ruptured basilar artery aneurysm who developed severe bilateral internal carotid artery vasospasm requiring bilateral balloon angioplasty. Prior to discharge, the patient's bilateral stenosis had improved. Three months post-discharge, severe restenosis in her bilateral internal carotid arteries occurred; a rare event. Balloon angioplasty has been demonstrated to histologically tear and stretch collagen fibers in the vessel wall and overexpansion of vessels may lead to a neo-intimal reaction that is similar to the one seen after stent placement in the intracranial circulation. Clinicians should be aware of the possibility of delayed and progressive stenosis in vessels treated with angioplasty. Follow-up vascular imaging is necessary after subarachnoid hemorrhage. Future study is required on the treatment paradigms necessary for this delayed restenosis.

A review of the combined medical and surgical management in patients with herpes simplex encephalitis.

BACKGROUND: Herpes simplex encephalitis (HSE) is a devastating and severe viral infection of the human central nervous system. This viral encephalitis is well known to cause severe cerebral edema and hemorrhagic necrosis with resultant increases in intracranial pressure (ICP). While medical management has been standardized in the treatment of this disease, the role of aggressive combined medical and surgical management including decompressive craniectomy and/or temporal lobectomy has not been fully evaluated. In addition, while barbiturate coma has been studied for treatment of status epilepticus associated with infectious encephalitis, its use for treatment of encephalitis associated intractable intracranial hypertension has not been fully reported. CASE DESCRIPTION: We report the case of a 22 year old female with severe herpetic encephalitis requiring aggressive ICP management utilizing all modalities (both medical and surgical) known to control ICP. She continues to have memory deficits but has made a good recovery with a Glasgow Outcome Scale score of 5. CONCLUSION: We provide evidence that aggressive combined medical and surgical therapy is warranted even in cases of severe HSE with transtentorial herniation, as there is evidence for the potential of good recovery. A detailed literature review of the medical and surgical management strategies in this disease is presented.

Enterprise stenting for intracranial aneurysm treatment induces dynamic and reversible age-dependent stenosis in cerebral arteries.

BACKGROUND: Although intracranial stenting has been associated with in-stent stenosis, the vascular response of cerebral vessels to the deployment of the Enterprise vascular reconstruction device is poorly defined. OBJECTIVE: To evaluate the change in parent vessel caliber that ensues after Enterprise stent placement. METHODS: Seventy-seven patients with 88 aneurysms were treated using Enterprise stent-assisted coil embolization and underwent high-resolution three-dimensional rotational angiography followed by three-dimensional edge-detection filtering to remove windowing-dependence measurement artifact. Orthogonal diameters and cross-sectional areas (CSAs) were measured proximal and distal on either side of the leading stent edge (points A, B), trailing stent edge (points D, E), and at mid-stent (point C). RESULTS: Enterprise stent deployment caused an instant increase in the parent artery CSA by 8.98% at D, which was followed 4-6 months later by significant in-stent stenosis (15.78% at A, 27.24% at B, 10.68% at C, 32.12% at D, and 28.28% at E) in the stented artery. This time-dependent phenomenon showed resolution which was complete by 12-24 months after treatment. This target vessel stenosis showed significant age dependence with greater response in the young. No flow-limiting stenosis requiring treatment was observed in this series. CONCLUSIONS: Use of the Enterprise stent is associated with a significant dynamic and spontaneously resolvable age-dependent in-stent stenosis. Further study is warranted on the clinical impact, if any, of this occurrence.

Widening of the basilar bifurcation angle: association with presence of intracranial aneurysm, age, and female sex.

OBJECT: Arterial bifurcations represent preferred locations for aneurysm formation, especially when they are associated with variations in divider geometry. The authors hypothesized a link between basilar apex aneurysms and basilar bifurcation (α) and vertebrobasilar junction (VBJ) angles. METHODS: The α and VBJ angles were measured in 3D MR and rotational angiographic volumes using a coplanar 3-point technique. Angle α was compared between age-matched cohorts in 45 patients with basilar artery (BA) aneurysms, 65 patients with aneurysms in other locations (non-BA), and 103 nonaneurysmal controls. Additional analysis was performed in 273 nonaneurysmal controls. Computational fluid dynamics (CFD) simulations were performed on parametric BA models with increasing angles. RESULTS: Angle α was significantly wider in patients with BA aneurysms (146.7° ± 20.5°) than in those with non-BA aneurysms (111.7° ± 18°) and in controls (103° ± 20.6°) (p < 0.0001), whereas no difference was observed for the VBJ angle. A wider angle α correlated with BA aneurysm neck width but not dome size, which is consistent with CFD results showing a widening of the impingement zone at the bifurcation apex. BA bifurcations hosting even small aneurysms (< 5 mm) had a significantly larger α angle compared with matched controls (p < 0.0001). In nonaneurysmal controls, α increased with age (p < 0.0001), with a threshold effect above 35 years of age and a steeper dependence in females (p = 0.002) than males (p = 0.04). CONCLUSIONS: The α angle widens with age during adulthood, especially in females. This angular widening is associated with basilar bifurcation aneurysms and may predispose individuals to aneurysm initiation by diffusing the flow impingement zone away from the protective medial band region of the flow divider.

Widening and high inclination of the middle cerebral artery bifurcation are associated with presence of aneurysms.

BACKGROUND AND PURPOSE: The middle cerebral artery (MCA) bifurcation is a preferred site for aneurysm formation. Wider bifurcation angles have been correlated with increased risk of aneurysm formation. We hypothesized a link between the presence of MCA aneurysms and the angle morphology of the bifurcation. METHODS: Three-dimensional rotational angiography volumes of 146 MCA bifurcations (62 aneurysmal) were evaluated for angle morphology: parent-daughter angles (larger daughter Ф1, smaller daughter Ф2), bifurcation angle (Ф1+Ф2), and inclination angle (γ) between the parent vessel axis and the plane determined by daughter vessel axes. Statistics were evaluated using Wilcoxon rank-sum analysis and area under the receiver operator characteristic curve. RESULTS: Aneurysmal bifurcations had wider inclination angle γ (median 57.8° versus 15.4°; P<0.0001). Seventy-five percent of aneurysmal MCAs had γ >10°, compared with 25% nonaneurysmal. Ф1 and Ф2, but especially Ф1+Ф2, were significantly larger in aneurysmal bifurcations (median 171.3° versus 98.1°; P<0.0001). Sixty-seven percent of aneurysmal bifurcations had Ф1+Ф2 >161°, compared with 0% nonaneurysmal MCAs. An optimal threshold of 140° was established for Ф1+Ф2 (area under the curve, 0.98). Sixty-eight percent of aneurysms originated off the daughter branches. Seventy-six percent of them originated off the branch with the largest branching angle, specifically if this was the smaller daughter branch. Wider Ф1+Ф2 correlated with aneurysm neck width, but not dome size. CONCLUSIONS: MCA bifurcations harboring aneurysms have significantly larger branching angles and more often originate off the branch with the largest angle. Wider inclination angle is strongly correlated with aneurysm presence, a novel finding. The results point to altered wall shear stress regulation as a possible factor in aneurysm development and progression.

Curvature effect on hemodynamic conditions at the inner bend of the carotid siphon and its relation to aneurysm formation.

Although high-impact hemodynamic forces are thought to lead to cerebral aneurysmal change, little is known about the aneurysm formation on the inner aspect of vascular bends such as the internal carotid artery (ICA) siphon where wall shear stress (WSS) is expected to be low. This study evaluates the effect of vessel curvature and hemodynamics on aneurysm formation along the inner carotid siphon. Catheter 3D-rotational angiographic volumes of 35 ICA (10 aneurysms, 25 controls) were evaluated in 3D for radius of curvature and peak curvature of the siphon bend, followed by univariate statistical analysis. Computational fluid dynamic (CFD) simulations were performed on patient-derived models after aneurysm removal and on synthetic variants of increasing curvature. Peak focal siphon curvature was significantly higher in aneurysm bearing ICAs (0.36 ± 0.045 vs. 0.30 ± 0.048 mm(-1), p=0.003), with no difference in global radius of curvature (p=0.36). In CFD simulations, increasing parametric curvature tightness (from 5 to 3mm radius) resulted in dramatic increase of WSS and WSS gradient magnitude (WSSG) on the inner wall of the bend. In patient-derived data, the location of aneurysms coincided with regions of low WSS (<4 Pa) flanked by high WSS and WSSG peaks. WSS peaks correlated with the aneurysm neck. In contrast, control siphon bends displayed low, almost constant, WSS and WSSG profiles with little spatial variation. High bend curvature induces dynamically fluctuating high proximal WSS and WSSG followed by regions of flow stasis and recirculation, leading to local conditions known to induce destructive vessel wall remodeling and aneurysmal initiation.

Superior performance of cone-beam CT angiography in characterization of intracranial atherosclerosis.

OBJECT: Intracranial atherosclerotic disease (ICAD) carries a high risk of stroke. Evaluation of ICAD has focused on assessing the absolute degree of stenosis, although plaque morphology has recently demonstrated increasing relevance. The authors provide the first report of the use of ultra-high-resolution C-arm cone-beam CT angiography (CBCT-A) in the evaluation of vessel stenosis as well as plaque morphology. METHODS: Between August 2009 and July 2012, CBCT-A was used in all patients with ICAD who underwent catheter-based angiography at the authors' institution (n = 18). Lesions were evaluated for maximum degree of stenosis as well as plaque morphological characteristics (ulcerated, calcified, dissected, or spiculated) via digital subtraction angiography (DSA), 3D-rotational angiography (3DRA), and CBCT-A. The different imaging modalities were compared in their assessment of absolute stenosis as well as their ability to resolve different plaque morphologies. RESULTS: Lesions were found to have similar degrees of stenosis when utilizing CBCT-A compared with 3DRA, but both 3DRA and CBCT-A differed from DSA in their assessment of the absolute degree of stenosis. CBCT-A provided the most detailed resolution of plaque morphology, identifying a new plaque characteristic in 61% of patients (n = 11) when compared with DSA and 50% (n = 9) when compared with 3DRA. CBCT-A identified all lesion characteristics visualized on DSA and 3DRA. CONCLUSIONS: CBCT-A provides detailed spatial resolution of plaque morphology and may add to DSA and 3DRA in the evaluation of ICAD. Further prospective study is warranted to determine any benefit CBCTA-A may provide in clinical decision making and risk stratification over existing conventional imaging modalities.