Monoclonal Antibodies: What the Diagnostic Neuroradiologist Needs to Know.

Monoclonal antibodies have become increasingly popular as novel therapeutics against a variety of diseases due to their specificity, affinity, and serum stability. Due to the nearly infinite repertoire of monoclonal antibodies, their therapeutic use is rapidly expanding, revolutionizing disease course and management, and what is now considered experimental therapy may soon become approved practice. Therefore, it is important for radiologists, neuroradiologists, and neurologists to be aware of these drugs and their possible different imaging-related manifestations, including expected and adverse effects of these novel drugs. Herein, we review the most commonly used monoclonal antibody-targeted therapeutic agents, their mechanism of action, clinical applications, and major adverse events with a focus on neurologic and neurographic effects and discuss differential considerations, to assist in the diagnosis of these conditions.

Symptomatic Developmental Venous Anomaly: State-of-the-Art Review on Genetics, Pathophysiology, and Imaging Approach to Diagnosis.

Developmental venous anomalies (DVAs) are the most common slow-flow venous malformation in the brain. Most DVAs are benign. Uncommonly, DVAs can become symptomatic, leading to a variety of different pathologies. DVAs can vary significantly in size, location, and angioarchitecture, and imaging evaluation of symptomatic developmental venous anomalies requires a systematic approach. In this review, we aimed to provide neuroradiologists with a succinct overview of the genetics and categorization of symptomatic DVAs based on the pathogenesis, which forms the foundation for a tailored neuroimaging approach to assist in diagnosis and management.

Learning Curve for Flow Diversion of Posterior Circulation Aneurysms: A Long-Term International Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Flow diversion has gradually become a standard treatment for intracranial aneurysms of the anterior circulation. Recently, the off-label use of the flow diverters to treat posterior circulation aneurysms has also increased despite initial concerns of rupture and the suboptimal results. This study aimed to explore the change in complication rates and treatment outcomes across time for posterior circulation aneurysms treated using flow diversion and to further evaluate the mechanisms and variables that could potentially explain the change and outcomes. MATERIALS AND METHODS: A retrospective review using a standardized data set at multiple international academic institutions was performed to identify patients with ruptured and unruptured posterior circulation aneurysms treated with flow diversion during a decade spanning January 2011 to January 2020. This period was then categorized into 4 intervals. RESULTS: A total of 378 procedures were performed during the study period. Across time, there was an increasing tendency to treat more vertebral artery and fewer large vertebrobasilar aneurysms (P = .05). Moreover, interventionalists have been increasingly using fewer overlapping flow diverters per aneurysm (P = .07). There was a trend toward a decrease in the rate of thromboembolic complications from 15.8% in 2011-13 to 8.9% in 2018-19 (P = .34). CONCLUSIONS: This multicenter experience revealed a trend toward treating fewer basilar aneurysms, smaller aneurysms, and increased usage of a single flow diverter, leading to a decrease in the rate of thromboembolic and hemorrhagic complications.

Endovascular Management of Intracranial Dural Arteriovenous Fistulas: Transarterial Approach.

In this second of 3 review articles on the endovascular management of intracranial dural AVFs, we discuss transarterial treatment approaches. The treatment goal is to occlude the fistulous point, including the most distal portion of the arterial supply together with the most proximal portion of the draining vein (ie, the "foot" of the vein), which can be accomplished with liquid embolic agents via transarterial access. Anatomic factors to consider when assessing the safety and efficacy of a transarterial approach using liquid embolic agents include location, angioarchitecture, and proximity of arterial feeders to both the vasa nervosum of adjacent cranial nerves and the external carotid-internal carotid/vertebral artery anastomoses. Anatomic locations typically favorable for transarterial approaches include but are not limited to the transverse/sigmoid sinus, cerebral convexity, and superior sagittal sinus. In this review article, we discuss the technical approaches, outcomes, potential complications, and complication avoidance strategies for transarterial embolization.

Endovascular Management of Intracranial Dural AVFs: Transvenous Approach.

In this third review article on the endovascular management of intracranial dural AVFs, we discuss transvenous embolization approaches. Transvenous embolization is increasingly popular and now the first-line approach for ventral dural AVFs involving the cavernous sinus and hypoglossal canal. In addition, transvenous embolization is increasingly used in lateral epidural dural AVFs in high-risk locations such as the petrous and ethmoid regions. The advantage of transvenous embolization in these locations is the ability to retrogradely embolize the draining vein and fistula while reducing the risk of ischemic cranial neuropathy or brain parenchymal infarction commonly feared from a transarterial approach. By means of coils ± ethylene-vinyl alcohol copolymer, transvenous embolization can achieve angiographic cure rates of 80%-90% in ventral locations. Potential complications include transient cranial neuropathy, neurologic deterioration due to venous outflow obstruction, and perforation while navigating pial veins. Transvenous embolization should be considered when dural AVFs arise in proximity to the vasa nervosum or extracranial-intracranial anastomoses.

Endovascular Management of Intracranial Dural AVFs: Principles.

Intracranial dural AVFs are abnormal communications between arteries that supply the dura mater and draining cortical veins or venous sinuses. They are believed to form as a response to venous insults such as thrombosis, trauma, or infection. Classification and management are dependent on the presence of drainage/reflux into cortical veins because such drainage markedly elevates the risk of hemorrhage or venous congestion, resulting in neurologic deficits. AVFs with tolerable symptoms and benign drainage patterns can be managed conservatively. Intolerable symptoms, presentation with hemorrhage/neurologic deficits, or aggressive drainage patterns are indications for intervention. Treatment options include microsurgical disconnection, endovascular transarterial embolization, transvenous embolization, or a combination. This is the first in a series of 3 articles on endovascular management of intracranial dural AVFs, in which we outline the principles and outcomes of endovascular treatment.

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia.

BACKGROUND: Approximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors. We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up. METHODS: 1637 HHT patients (342 with brain VMs) were recruited from 14 HHT centres of the Brain Vascular Malformation Consortium since 2010 and followed prospectively (mean = 3.4 years). We tested whether the presence of brain VM, other HHT organ involvement, and HHT mutation genotype were associated with worse mRS scores at baseline and during follow-up, using linear mixed models, adjusting for age, sex, and year of visit. RESULTS: Presence of brain VMs was not associated with worse mRS score at baseline and there was no significant worsening of mRS with prospective follow-up in these patients; 92% had baseline mRS of 0-2. HHT-related gastrointestinal (GI) bleeding was associated with worse mRS scores at baseline (0.37, 95% CI 0.26-0.47, p < 0.001), as were history of anemia (0.35, 95% CI 0.27-0.43, p < 0.001) and liver VMs (0.19, 95% CI 0.09-0.30, p < 0.001). Presence of pulmonary arteriovenous malformations (AVMs) was not associated with worse mRS scores at baseline. mRS score was not associated with either HHT genotype (Endoglin vs ACVRL1). Only GI bleeding was associated with a significantly worsening mRS during prospective follow-up (0.64, 95% CI 0.21-1.08, p = 0.004). CONCLUSION: Most HHT-brain VM patients had good functional capacity (mRS scores 0-2) at baseline that did not change significantly over 3.4 mean years of follow-up, suggesting that mRS may not be useful for predicting or measuring outcomes in these patients. However, HHT patients with GI bleeding, anemia history or liver VMs had worse mRS scores, suggesting significant impact of these manifestations on functional capacity. Our study demonstrates the insensitivity of the mRS as an outcomes measure in HHT brain VM patients and reinforces the continued need to develop outcomes measures, and their predictors, in this group.

Ticagrelor versus Clopidogrel in the Dual Antiplatelet Regimen for Intracranial Stenting or Flow-Diverter Treatment for Unruptured Cerebral Aneurysms: A Single-Center Cohort Study.

BACKGROUND AND PURPOSE: Ticagrelor is a novel P2Y12 antagonist, and little is known about its efficacy and safety in the endovascular treatment of aneurysms. This study evaluated the efficacy and safety of ticagrelor versus clopidogrel for stent-assisted coiling or flow-diversion treatment in patients with unruptured cerebral aneurysms. MATERIALS AND METHODS: From November 2003 to February 2019, two hundred one patients (mean age, 57.5 years; 156 women) with 233 unruptured aneurysms underwent stent-assisted coiling or flow-diversion treatment. All patients received antiplatelet therapy of aspirin plus clopidogrel (clopidogrel group, 121 patients with 140 aneurysms) or aspirin plus ticagrelor (ticagrelor group, 80 patients with 93 aneurysms). The clinical and radiologic data in each group were retrospectively reviewed and compared. RESULTS: Two hundred thirty-six procedures were performed, including stent-assisted coiling (n = 101) and flow diversion (n = 135). At 90 days, the primary outcome-a composite of any stroke and death-occurred in 9.9% of the clopidogrel group and 8.6% of the ticagrelor group (P = .822). Ischemic stroke occurred in 10 (7.0%) of the clopidogrel group and 7 (7.5%) of the ticagrelor group (P > .999). Disabling stroke occurred in 4 (2.8%) in the clopidogrel group and in 4 (4.3%) in the ticagrelor group (P = .716). Ninety-day death occurred in 3 (2.1%) in the clopidogrel group and 1 (1.1%) in the ticagrelor group (P > .999). Any bleeding at 90 days occurred in 13 (9.2%) in the clopidogrel group and 6 (6.5%) in the ticagrelor group (P = .479). CONCLUSIONS: Ticagrelor appears to be as effective and safe as clopidogrel in stent-assisted coiling or flow-diversion treatment for unruptured cerebral aneurysms.

Differential Contribution of ASPECTS Regions to Clinical Outcome after Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Ischemic stroke is the leading cause of long-term disability in adults, but our ability to prognosticate from baseline imaging data is limited. The ASPECTS measures ischemic change in the middle cerebral artery territory on noncontrast CT based on 10 anatomic regions. Here, we investigated whether infarction in particular regions was associated with worse long-term outcome. MATERIALS AND METHODS: We identified consecutive patients receiving mechanical thrombectomy for ICA/MCA occlusion at 2 comprehensive stroke centers. Pretreatment ASPECTS was assessed by 2 blinded reviewers. Clinical data including demographics, baseline NIHSS score, and 90-day mRS were collected. The relationship between individual ASPECTS regions and the mRS score (0-2 versus 3-6) was assessed using multivariable logistic regression. RESULTS: Three hundred fifty-three patients were included (mean age, 70 years; 46% men), of whom 214 had poor outcome (mRS = 3-6). Caudate (OR = 3.26; 95% CI, 1.33-8.82), M4 region (OR = 2.94; 95% CI, 1.09-9.46), and insula (OR = 1.75; 95% CI, 1.08-2.85) infarcts were associated with significantly greater odds of poor outcome, whereas M1 region infarction reduced the odds of poor outcome (OR = 0.38; 95% CI, 0.14-0.99). This finding remained unchanged when restricted to only patients with good recanalization. No significant associations were found by laterality. Similarly, no region was predictive of neurologic improvement during the first 24 hours or of symptomatic intracerebral hemorrhage. CONCLUSIONS: Our results indicate that ASPECTS regions are not equal in their contribution to functional outcome. This finding suggests that patient selection based on total ASPECTS alone might be insufficient, and infarct topography should be considered when deciding eligibility for thrombectomy.

Neuroimaging Findings in Patients with COVID-19.

Little is known about the neurologic sequelae of coronavirus disease 2019 (COVID-19). We assessed neuroimaging findings in 4 patients positive for COVID-19. All had abnormal mental status, deranged coagulation parameters, and markedly elevated D-dimer levels. CT/MR imaging showed a common pattern of multifocal subcortical/cortical petechial-type hemorrhages, while SWI showed more extensive multifocal abnormalities. The appearances are consistent with a thrombotic microangiopathy and may be due to the heightened level of thrombosis in patients with COVID-19.

Facial Nerve Arterial Arcade Supply in Dural Arteriovenous Fistulas: Anatomy and Treatment Strategies.

BACKGROUND AND PURPOSE: Endovascular treatment of petrous dural AVFs may carry a risk of iatrogenic facial nerve palsy if the facial nerve arterial arcade, an anastomotic arterial arch that supplies the geniculate ganglion, is not respected or recognized. Our purpose was to demonstrate that the use of a treatment strategy algorithm incorporating detailed angiographic anatomic assessment allows identification of the facial nerve arterial arcade and therefore safe endovascular treatment. MATERIALS AND METHODS: This was a retrospective cohort study of consecutive petrous dural AVF cases managed at Toronto Western Hospital between 2006 and 2018. Our standard of care consists of detailed angiographic assessment followed by multidisciplinary discussion on management. Arterial supply, primary and secondary treatments undertaken, angiographic outcomes, and clinical outcomes were assessed by 2 independent fellowship-trained interventional neuroradiologists. RESULTS: Fifteen patients had 15 fistulas localized over the petrous temporal bone. Fistulas in all 15 patients had direct cortical venous drainage and received at least partial supply from the facial nerve arterial arcade. Following multidisciplinary evaluation, treatment was performed by endovascular embolization in 8 patients (53%) and microsurgical disconnection in 7 patients (47%). All patients had long-term angiographic cure, and none developed iatrogenic facial nerve palsy. CONCLUSIONS: By means of our treatment strategy based on detailed angiographic assessment and multidisciplinary discussion, approximately half of our patients with petrous AVFs were cured by endovascular treatment, half were cured by an operation, and all had preserved facial nerve function.

Artery of Davidoff and Schechter Supply in Dural Arteriovenous Fistulas.

The artery of Davidoff and Schechter is a dural branch of the posterior cerebral artery that can supply the meninges close to the falcotentorial junction. It is usually not identified on angiography except when enlarged in the setting of a dural AVF or meningioma. The impact on treatment of the artery of Davidoff and Schechter supply to a fistula is not well-described in the literature. Our retrospective analysis of patients with dural AVFs treated at the Toronto Western Hospital between 2006 and 2018 identified 6 patients with dural AVFs receiving supply from artery of Davidoff and Schechter (of a total of 173 patients with dural AVFs). All patients were initially treated by transarterial embolization using liquid embolic agents. Three patients required a second endovascular procedure partly due to residual supply from artery of Davidoff and Schechter, and in all cases, angiographic cure was obtained. The treatment approach, challenges encountered, and potential complications of treating such fistulas are described.

Acute Cortical Lesions in MELAS Syndrome: Anatomic Distribution, Symmetry, and Evolution.

BACKGROUND AND PURPOSE: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder affecting children and young adults. Stroke-like episodes are often associated with acute cortical lesions in the posterior cerebral cortex and are classically described as asymmetric and transient. In this study we assessed the anatomic distribution of acute cortical lesions, the incidence of symmetry, and the temporal evolution of lesions. MATERIALS AND METHODS: This was a retrospective cohort study of patients who had a confirmed genetic diagnosis of a pathogenic variant associated with MELAS and MR imaging performed at our center (2006-2018). Each MR imaging study was assessed for new lesions using T1, T2, FLAIR, DWI, ADC, and SWI. The anatomic location, symmetry, and temporal evolution of lesions were analyzed. RESULTS: Eight patients with the same pathogenic variant of MELAS (MT-TL1 m.3243A>G) with 31 MR imaging studies were included. Forty-one new lesions were identified in 17 of the studies (5 deep, 36 cortical). Cortical lesions most commonly affected the primary visual cortex, the middle-third of the primary somatosensory cortex, and the primary auditory cortex. Thirty of 36 cortical lesions had acute cortical diffusion restriction, of which 21 developed cortical laminar necrosis on subacute imaging. Six of 11 studies with multiple lesions showed symmetric cortical involvement. CONCLUSIONS: Acute cortical lesions in MELAS most commonly affect the primary visual, somatosensory, and auditory cortices, all regions of high neuronal density and metabolic demand. The most common pattern of temporal evolution is acute cortical diffusion restriction with subacute cortical laminar necrosis and chronic volume loss. Symmetric involvement is more common than previously described.

Decreased Subcortical T2 FLAIR Signal Associated with Seizures.

Abnormally decreased T2/T2 FLAIR signal can be seen on brain imaging of patients who are experiencing clinical or subclinical seizures and can be associated with various intracranial pathologies. We identified 29 such patients. The abnormal signal was unilateral in 75.9% of patients. It affected various lobes of the brain, but only in the anterior circulation. In 28 patients (96.6%), there was corresponding decreased signal on DWI. The ADC was normal in all cases. In 26 patients (89.7%), there was corresponding low signal on SWI/gradient recalled-echo; 44.8% of patients underwent contrast-enhanced scans, and there was no abnormal enhancement. Twenty-two (75.9%) patients had documented clinical seizures on the day of imaging. The most frequent concomitant pathology was a subdural hematoma. Electroencephalograms obtained within 24 hours of imaging were available in 65.5%. Findings of all of these electroencephalograms were abnormal, and these electroencephalogram changes were either localized to the area of the abnormal MR imaging signal (where the signal was unilateral) or were bilateral (where the MR imaging changes were bilateral). In summary, decreased white matter T2/T2 FLAIR signal changes can be seen in patients with remarkably similar clinical findings (particularly seizures). These changes are often correlated with abnormal electroencephalogram activity localized to the involved lobes.

Sentinel Angiographic Signs of Cerebral Hyperperfusion after Angioplasty and Stenting of Intracranial Atherosclerotic Stenosis: A Technical Note.

Cerebral hyperperfusion syndrome is a serious complication of endovascular angioplasty and stent placement for long-standing intracranial stenosis, resulting in neurologic dysfunction, seizure, or reperfusion hemorrhage. Rigorous control of blood pressure is commonly used in the perioperative period to prevent cerebral hyperperfusion syndrome, but the optimal blood pressure is often arbitrary. We describe the angiographic features that reflect impaired cerebral autoregulation and microvascular transit abnormality, which may be used to gauge the optimal blood pressure parameters in the immediate postintervention period for prevention of cerebral hyperperfusion syndrome.

Predictive Value of MRI in Diagnosing Brain AVM Recurrence after Angiographically Documented Exclusion in Children.

BACKGROUND AND PURPOSE: MRI is routinely performed following brain AVM after treatment in children. Our aim was to determine the predictive values of contrast-enhanced MR imaging and TOF-MRA for brain AVM recurrence in children, compared with conventional angiography and the role of 3D rotational angiography-MR imaging fusion in these cases. MATERIALS AND METHODS: We included all pediatric patients with brain AVMs during an 18-year period with angiographically documented obliteration after treatment. Patients underwent 3T MR imaging, including contrast-enhanced MR imaging, TOF-MRA, and conventional angiography, with a subset undergoing 3D rotational angiography. The predictive values of contrast-enhanced MR imaging and TOF-MRA for brain AVM recurrence were determined. CTA sections reconstructed from 3D rotational angiography were coregistered with and fused to 3D-T1WI for analysis. RESULTS: Thirty-nine children (10.8 ± 3.9 years of age; range, 2-17 years; male/female ratio, 19:20; mean Spetzler-Martin grade, 1.9 ± 0.6) met the inclusion criteria. Of these, 13 had angiographically confirmed brain AVM recurrence, 8 following surgery and 5 following embolization. Sensitivity, specificity, and positive and negative predictive values for recurrence were the following: contrast-enhanced MR imaging: 84.6%, 38.5%, 40.7%, 81.8%; TOF-MRA: 50.0%, 96.1%, 85.7%, 79.3%; both: 75.0%, 90.9%, 85.7%, 83.3%. 3D rotational angiography-MR imaging fused images confirmed or excluded recurrence in all available cases (13/13). Embolization-only treatment was a significant predictor of recurrence (OR = 32.4, P = .006). MR imaging features predictive of recurrence included a tuft of vessels on TOF-MRA and nodular juxtamural/linear enhancement with a draining vein on contrast-enhanced MR imaging. CONCLUSIONS: MR imaging is useful for surveillance after brain AVM treatment in children, but conventional angiography is required for definitive diagnosis of recurrence. TOF-MRA and contrast-enhanced MR imaging provide complementary information for determining brain AVM recurrence and should be interpreted in conjunction. 3D rotational angiography-MR imaging fusion increases the diagnostic confidence regarding brain AVM recurrence and is therefore suited for intraoperative neuronavigation.

A new multi-channel Mach probe measuring the radial ion flow velocity profile in the boundary plasma of the W7-X stellarator.

Ion flow velocity measurement in the edge and scraper-off layer region is beneficial to understand the confinement related phenomenon in fusion devices such as impurity transport and plays an important role in impurity control. During the Wendelstein 7-X (W7-X) operation phase 1.2a, a multi-channel (MC) Mach probe mounted on the multi-purpose manipulator has been used to measure radial profiles of edge ion flow velocity. This MC-Mach probe consists of two polar and two radial arrays of directional Langmuir pins (28 pins in total) serving for different aims, of which the polar arrays could obtain a polar distribution of ion saturation current, while the radial arrays can be used to study the dynamic process of a radially propagated event. In this paper, we report the observation of the radially outward propagation of a low frequency mode with a speed of around 200 m/s. The first measurement of the radial ion flow velocity profile using the MC-Mach probe in the boundary plasma of the W7-X with an island divertor will also be presented.