Management of Intracranial Stenotic Disease in Cancer Patients Treated With Vasotoxic Agents.

OBJECTIVE: To summarize the characteristics of and therapeutic options for cancer patients whose treatments may be vasotoxic and cause intracranial arterial stenotic disease and stroke. METHODS: We describe 3 patients with symptomatic cerebrovascular pathology that were being actively treated for cancer. RESULTS: Two of the patients were being treated with tyrosine kinase inhibitors (TKIs); and the third was being treated with 2 monoclonal antibodies, one of which was targeting an endothelial growth factor. These agents have been associated with vascular adverse events. Surgical revascularization was done in the first 2 patients, as they were suffering from cerebral ischemia. The third patient had suffered a significant brain hemorrhage, and therapeutic options were limited. In the first 2 patients, treatments also included antiplatelet agents and stopping/changing the TKI. In one of these patients we demonstrated regression of arterial stenosis after changing the TKI. CONCLUSIONS: Possibilities for treatment in this population, beyond the usual medical and surgical administrations, may include stopping or changing cancer drugs that may be related to the development of arterial pathology. Collaboration with oncologists is essential in this subset of patients. While aware of the potential for vascular toxicity, oncologists are often not fully appreciative of the fact that their therapeutic agents can cause stroke.

Infusion warm during selective hypothermia in acute ischemic stroke.

INTRODUCTION: Mechanical thrombectomy (MT) has dramatically improved the prognosis for acute ischemic stroke (AIS) patients. Despite high recanalization rates, up to half of the patients will not present a good neurological outcome after MT. Therapeutic hypothermia is perhaps the most robust neuroprotectant studied preclinically. MATERIALS AND METHODS: We explored various warming effects that can reduce the effectiveness or potency of selective hypothermia during AIS under conditions similar to actual clinical care. Four different selective hypothermia layouts were chosen. Layouts 1 and 2 used a single catheter without and with an insulated IV bag. Layouts 3 and 4 used two catheters arrange coaxially, without and with an insulated IV bag. Independent variables measured were IV bag exit temperature, catheter inlet temperature, and catheter outlet temperature at four different flow rates ranging from 8 to 25 ml/min over an infusion duration of 20 min. RESULTS: Dominant warming occurs along the catheter pathway compared to warming along the infusion line pathway, ranging from 66% to 72%. Coaxial configurations provided an approximate 4°C cooler temperature benefit on delivered infusate over a single catheter. Brain tissue temperature predictions show that the maximum cooling layout, Layout 4 at maximum flow provides a 1°C within 5 min. CONCLUSION: Significant rewarming effects occur along the infusate flow path from IV bag to site of injury in the brain. Previous selective hypothermia clinical work, using flow rates and equipment at conditions similar to our study, likely produced rapid but not deep tissue cooling in the brain (~ 1°C).

Neuro-Interventional Management of Acute Ischemic Stroke.

Restoration of cerebral blood flow is the most important step in preventing irreversible damage to hypoperfused brain cells after ischemic stroke from large-vessel occlusion. For those patients who do not respond to (or are not eligible for) intravenous thrombolysis, endovascular therapy has become standard of care. A shift is currently taking place from rigid time windows for intervention (time is brain) to physiology-driven paradigms that rely heavily on neuroimaging. At this time, one can reasonably anticipate that more patients will be treated, and that outcomes will keep improving. This article discusses in detail recent advances in endovascular stroke therapy.

e-ASPECTS software is non-inferior to neuroradiologists in applying the ASPECT score to computed tomography scans of acute ischemic stroke patients.

Background The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is an established 10-point quantitative topographic computed tomography scan score to assess early ischemic changes. We performed a non-inferiority trial between the e-ASPECTS software and neuroradiologists in scoring ASPECTS on non-contrast enhanced computed tomography images of acute ischemic stroke patients. Methods In this multicenter study, e-ASPECTS and three independent neuroradiologists retrospectively and blindly assessed baseline non-contrast enhanced computed tomography images of 132 patients with acute anterior circulation ischemic stroke. Follow-up scans served as ground truth to determine the definite area of infarction. Sensitivity, specificity, and accuracy for region- and score-based analysis, receiver-operating characteristic curves, Bland-Altman plots and Matthews correlation coefficients relative to the ground truth were calculated and comparisons were made between neuroradiologists and different pre-specified e-ASPECTS operating points. The non-inferiority margin was set to 10% for both sensitivity and specificity on region-based analysis. Results In total 2640 (132 patients × 20 regions per patient) ASPECTS regions were scored. Mean time from onset to baseline computed tomography was 146 ± 124 min and median NIH Stroke Scale (NIHSS) was 11 (6-17, interquartile range). Median ASPECTS for ground truth on follow-up imaging was 8 (6.5-9, interquartile range). In the region-based analysis, two e-ASPECTS operating points (sensitivity, specificity, and accuracy of 44%, 93%, 87% and 44%, 91%, 85%) were statistically non-inferior to all three neuroradiologists (all p-values <0.003). Both Matthews correlation coefficients for e-ASPECTS were higher (0.36 and 0.34) than those of all neuroradiologists (0.32, 0.31, and 0.3). Conclusions e-ASPECTS was non-inferior to three neuroradiologists in scoring ASPECTS on non-contrast enhanced computed tomography images of acute stroke patients.

Transarterial Embolization of a Spontaneous Intraorbital Arteriovenous Fistula With n-BCA Glue.

Arteriovenous fistulae of the orbit are exceedingly rare. They are high-flow vascular malformations involving a fistula from the ophthalmic artery to one of the draining ophthalmic veins. Presenting symptoms can mimic those of carotid cavernous fistulae or of ophthalmic venous varices, and include diplopia, proptosis, chemosis, decreased visual acuity, and retro-orbital pain. Very few case reports are published on the treatment of this aggressive vascular malformation, and they uniformly describe techniques involving a transvenous access for the embolization of the fistula. To the best of authors' knowledge, they report the first case of transarterial embolization of an intraorbital AVF.

Subarachnoid Hemorrhage Following Angioplasty and Stenting in a Patient with Primitive Drainage Pattern of the Basal Vein of Rosenthal.

Severe visual loss may occur in patients with pseudotumor cerebri (PTC), also known as idiopathic intracranial hypertension. Transverse sinus stenosis is 1 cause of PTC syndrome. Although the role of transverse sinus stenosis in the pathogenesis of the disease remains controversial, recent case series of transverse sinus stenting have reported very high rates of symptom response and resolution of papilledema with improvement or at least stabilization of the visual fields and visual acuity (Ahmed et al., 2011).1 We report a previously unpublished complication of diffuse, nonaneurysmal subarachnoid hemorrhage following angioplasty and stenting in a patient with refractory PTC.

Clinical utility of quantitative magnetic resonance angiography in the assessment of the underlying pathophysiology in a variety of cerebrovascular disorders.

BACKGROUND: Quantitative MRA (qMRA) is a relatively new technique that uses traditional time-of-flight and phase-contrast MRI to visualize extracranial and intracranial vascular anatomy and measure volumetric blood flow. We aimed to assess the clinical utility of qMRA in assessing the hypothesized pathophysiology (HP) in a range of cerebrovascular diseases. Moreover, we postulated that evaluation of the arterial waveforms, can improve the evaluation of the hypothesized pathophysiology by qMRA. METHODS: We reviewed studies from 10 patients who underwent qMRA examinations before and after their treatments. Two reviewers assessed the anatomy, volumetric flow rates and arterial waveforms for each vessel sampled and reached a consensus as to whether the above parameters supported the clinical diagnosis/hypothesized pathophysiology and the subsequent management. FINDINGS: All 20 qMRA studies were technically adequate. qMRA supported the HP in all 10 patients as determined by abnormal volumetric flow values in the affected vessels before treatment and by the correction of these abnormal values in the patients whose treatment was successful. Each of our five patients with occlusive disease/vasoconstriction demonstrated evidence of dampening of the arterial waveforms distally to the narrowed artery (parvus-tardus phenomenon). The parvus-tardus effect disappeared after treatment. CONCLUSION: qMRA is unique in combining time-of-flight MRA in a complementary manner with phase-contrast MRA to obtain volumetric flow values and potentially important physiologic information from arterial waveform analysis in patients with a range of cerebrovascular diseases during the course of a single MR examination.

Congenital extrahepatic portosystemic shunts (Abernethy malformation): a histopathologic evaluation.

Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. Aside from the complete or near-complete absence of portal veins, other histologic features of Abernethy malformation have not been evaluated in the literature. The goal of this study was to detail the hepatic histopathology in 5 patients with Abernethy malformation diagnosed at our institution. Paraffin-embedded tissue sections from 1 explant, 2 liver tumor resections, and 2 liver biopsies were evaluated using hematoxylin and eosin stains, reticulin, elastic, and trichrome stains, and immunohistochemistry for D2-40. Histologic findings included absence of portal veins in small portal tracts, absent or hypoplastic portal veins in medium-sized and large-sized portal tracts, isolated capillaries and arterioles in the lobules, hypertrophy of hepatic artery branches, remodeling of the liver architecture, and nodular regenerative hyperplasia in 1 case. Two patients had hepatocellular carcinoma without cirrhosis, and 2 had focal nodular hyperplasia. In addition to loss of portal veins, Abernethy malformation is characterized by multiple abnormalities due to remodeling of the hepatic vasculature. Abernethy malformation may also be associated with hepatocellular carcinoma and focal nodular hyperplasia in some patients.

CT perfusion imaging in acute stroke.

Computed tomographic perfusion (CTP) imaging is an advanced modality that provides important information about capillary-level hemodynamics of the brain parenchyma. CTP can aid in diagnosis, management, and prognosis of acute stroke patients by clarifying acute cerebral physiology and hemodynamic status, including distinguishing severely hypoperfused but potentially salvageable tissue from both tissue likely to be irreversibly infarcted ("core") and hypoperfused but metabolically stable tissue ("benign oligemia"). A qualitative estimate of the presence and degree of ischemia is typically required for guiding clinical management. Radiation dose issues with CTP imaging, a topic of much current concern, are also addressed in this review.

Congenital portosystemic shunts: imaging findings and clinical presentations in 11 patients.

OBJECTIVE: To evaluate the clinical anatomy and presentations of congenital portosystemic shunts, and determine features that promote recognition on imaging. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study. The requirement for written informed consent was waived. Radiology reports were retrospectively reviewed from non-cirrhotic patients who underwent imaging studies from January 1999 through February 2009. Clinical sources reviewed included electronic medical records, archived images and histopathological material. RESULTS: Eleven patients with congenital portosystemic shunts were identified (six male and five female; age range 20 days to 84 years). Seven patients had extrahepatic and four patients had intrahepatic shunts. All 11 patients had absent or hypoplastic intrahepatic portal veins, a feature detected by CT and MRI, but not by US. Seven patients presented with shunt complications and four with presentations unrelated to shunt pathophysiology. Three adult patients had four splenic artery aneurysms. Prospective radiological evaluation of five adult patients with cross-sectional imaging had failed prospectively to recognize the presence of congenital portosystemic shunts on one or more imaging examinations. CONCLUSIONS: Congenital portosystemic shunts are associated with splenic artery aneurysms, a previously unrecognized association. Portosystemic shunts were undetected during prospective radiologic evaluation in the majority of adult patients, highlighting the need to alert radiologists to this congenital anomaly.

Connectivity alterations assessed by combining fMRI and MR-compatible hand robots in chronic stroke.

The aim of this study was to investigate functional reorganization of motor systems by probing connectivity between motor related areas in chronic stroke patients using functional magnetic resonance imaging (fMRI) in conjunction with a novel MR-compatible hand-induced, robotic device (MR_CHIROD). We evaluated data sets obtained from healthy volunteers and right-hand-dominant patients with first-ever left-sided stroke > or =6 months prior and mild to moderate hemiparesis affecting the right hand. We acquired T1-weighted echo planar and fluid attenuation inversion recovery MR images and multi-level fMRI data using parallel imaging by means of the GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) algorithm on a 3 T MR system. Participants underwent fMRI while performing a motor task with the MR_CHIROD in the MR scanner. Changes in effective connectivity among a network of primary motor cortex (M1), supplementary motor area (SMA) and cerebellum (Ce) were assessed using dynamic causal modeling. Relative to healthy controls, stroke patients exhibited decreased intrinsic neural coupling between M1 and Ce, which was consistent with a dysfunctional M1 to Ce connection. Stroke patients also showed increased SMA to M1 and SMA to cerebellum coupling, suggesting that changes in SMA and Ce connectivity may occur to compensate for a dysfunctional M1. The results demonstrate for the first time that connectivity alterations between motor areas may help counterbalance a functionally abnormal M1 in chronic stroke patients. Assessing changes in connectivity by means of fMRI and MR_CHIROD might be used in the future to further elucidate the neural network plasticity that underlies functional recovery in chronic stroke patients.

Functional MRI of Rehabilitation in Chronic Stroke Patients Using Novel MR-Compatible Hand Robots.

We monitored brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible, hand-induced, robotic device (MR_CHIROD). We evaluated 60 fMRI datasets on a 3 T MR system from five right-handed patients with left-sided stroke >/=6 months prior and mild to moderate hemiparesis. Patients trained the paretic right hand at approximately 75% of maximum strength with an exercise ball for 1 hour/day, 3 days/week for 4 weeks. Multi-level fMRI data were acquired before, during training, upon completion of training, and after a non-training period using parallel imaging employing GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) while the participant used the MR_CHIROD. Training increased the number of activated sensorimotor cortical voxels, indicating functional cortical plasticity in chronic stroke patients. The effect persisted four weeks after training completion, indicating the potential of rehabilitation in inducing cortical plasticity in chronic stroke patients.