1. Bonati LH, Jansen O, de Borst GJ, et al. Management of atherosclerotic extracranial carotid artery stenosis. Lancet Neurol 2022;21:273–83. Available from: http://dx.doi.org/10.1016/S1474-4422(21)00359-8

The benefit of carotid endarterectomy in patients with symptomatic carotid stenosis was established in the final two decades of the past century. In the NASCET trial, the 2-year risk of any ipsilateral stroke (including perioperative events) in patients with severe symptomatic carotid stenosis (≥70% narrowing of the lumen) was reduced from 26% to 9%. Modest benefit was also observed in patients with moderate stenosis (50–69%) by a reduction of stroke risk from 22.2% to 15.7% after 5 years. In the European Carotid Surgery Trial (ECST), endarterectomy prevented stroke only in patients with symptomatic carotid stenosis of 80% or greater, but measurement of the degree of stenosis on angiography differed between the trials. In a pooled analysis of NASCET, ECST, and the smaller Veterans Affairs trial, in which ECST angiograms were reanalyzed using the NASCET method, the absolute 5-year risk reduction from endarterectomy was 15.9% in patients with severe (≥70%) stenosis and 4.6% in patients with moderate (50–69%) stenosis. Thus, the number needed to treat would be six patients with severe symptomatic stenosis, or 22 patients with moderate symptomatic stenosis, had to be operated on to prevent one ipsilateral stroke after 5 years. Furthermore, extracranial-intracranial bypass surgery is not effective to prevent stroke in patients with carotid artery occlusion.

Among patients with symptomatic carotid stenosis, randomized controlled trials have consistently shown that the risk of periprocedural stroke or death is greater with stenting than with endarterectomy. However, this outcome was mainly caused by a higher risk of minor stroke occurring with stenting, and the extra events largely occurred in patients older than 70 years. Conversely, stenting reduces the risk of procedure-related myocardial infarction, cranial nerve palsy, and hematoma at the access site. Excluding periprocedural events, stenting and endarterectomy work equally well to prevent recurrent stroke or recurrence of stenosis. For patients in whom both stenting and endarterectomy are feasible (ie, symptomatic carotid stenosis), the choice of treatment should primarily be based on an assessment of procedural risks. Additionally, stenting might be considered in symptomatic patients at increased risk for complications with surgery, people in whom the stenosis occurred after previous surgery or after radiation therapy to the neck, and if the stenosis is not surgically accessible, provided these individuals are considered to benefit from revascularization. Stenting should not be routinely used to treat asymptomatic carotid stenosis but might be suggested in asymptomatic patients in whom revascularization is appropriate and who are less suitable for surgery.

4 panels and 2 figures with basic MR of embolic infarcts and CTA

2. Dobrocky T, Nicholson P, Häni L, et al. Spontaneous intracranial hypotension: searching for the CSF leak. Lancet Neurol 2022;21:369–80. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1474442221004233

Spontaneous intracranial hypotension is caused by loss of CSF at the level of the spine. The most frequent symptom of this disorder is orthostatic headache, with the headache worsening in the upright position and subsiding after lying down. Neuroimaging has a crucial role in diagnosing and monitoring spontaneous intracranial hypotension, because it provides objective (albeit often subtle) data despite the variable clinical syndromes and often normal lumbar puncture opening pressure associated with this disorder. Spine imaging aims to classify and localize the site of CSF leakage as either (1) a ventral dural leak, (2) a leaking spinal nerve root diverticulum, or (3) a direct CSF-venous fistula. Searching for a CSF leak can be very difficult; the entire spine must be scrutinized for a dural breach often the size of a pin. Precisely locating the site of CSF leakage is fundamental to successful treatment, which includes a targeted epidural patch and surgical closure or endovascular venous embolization when conservative measures do not provide long-term relief.  Conventional spine MRI has no localizing value, so a dynamic myelography technique with intrathecal contrast is generally required for leak localization. Intrathecal Gd-enhanced spine MRI is an off-label indication and should only be used for specific patients when alternative methods are not available. The spontaneous intracranial hypotension score (known as SIH score, aka Bern score, aka Dobrocky score) is a nine-point, brain MRI-based scale that denotes the likelihood of finding a spinal CSF leak in patients with clinically suspected spontaneous intracranial hypotension.

4 figures, 1 table

3. Pirson FAV, Boodt N, Brouwer J, et al. Endovascular treatment for posterior circulation stroke in routine clinical practice: results of the multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands Registry. Stroke 2022;53:758–68

The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This study evaluates outcomes of a large PCS cohort treated with EVT in clinical practice. Simultaneous to this observational study, several intervention centers participated in the BASICS trial (Basilar Artery International Cooperation Study), which tested the efficacy of EVT for basilar artery occlusion in a randomized setting. The authors additionally compared characteristics and outcomes of patients treated outside BASICS in trial centers to those from nontrial centers.

They included 264 patients of whom 135 (51%) had received intravenous thrombolysis. The basilar artery was most often involved (77%). Favorable outcome (modified Rankin Scale score 0–3) was observed in 115/252 (46%) patients, and 109/252 (43%) patients died. Successful reperfusion was achieved in 178/238 (75%), and symptomatic intracranial hemorrhage occurred in 9/264 (3%). The 154 nontrial patients receiving EVT in BASICS trial centers had similar characteristics and outcomes as the 110 patients treated in nontrial centers.

Regarding mortality within 90 days after EVT, they report a relatively high proportion (43%) compared with other PCS registries (28%–34%) but similar to several BAO registries (44%–47%). The authors think that the high mortality might be caused by the relatively high proportion of BAOs (77%) versus vertebral or posterior cerebral artery occlusions in their cohort. Furthermore, they found similar risk factors for worse outcome as in the anterior circulation stroke population treated with EVT.

3 tables, 2 figures, no imaging

4. Tsai H-H, Hsieh Y-C, Lin JS, et al. Functional investigation of meningeal lymphatic system in experimental intracerebral hemorrhage. Stroke 2022;53:987–98

ICH most commonly occurs due to rupture of the neurovascular unit that has been damaged by chronic hypertension or amyloid angiopathy. The subsequent release of blood components produces a dynamic, space-occupying intraparenchymal hematoma that is associated with mechanical brain architectural destruction, inflammatory responses, neurological complications, and poor clinical outcomes. Hematoma clearance through surgical removal or enhancement of endogenous hematoma resolution is a potential therapeutic target for treating ICH. Recently, the meningeal lymphatic system has been identified as a critical mediator of draining pathogenic substances including brain-derived antigens, immune cells, and amyloid-β out of the CNS.  However, whether the same system participates in modulation of intraparenchymal hematoma clearance and CNS pathologies after ICH remains unclear.

A total of 294 eight- to 12-week-old C57BL/6 (wild-type) male mice from the Jackson Laboratory were used in this study. Immunofluorescence of whole-mount meninges was used to measure complexity and coverage level of meningeal lymphatic vasculature following ICH induction. Fluorescent microbeads and PKH-26-labeled erythrocytes were used to evaluate drainage function of the meningeal lymphatic system. Visudyne treatment, deep cervical lymph node ligation, and VEGF (vascular endothelial growth factor)-C injection were performed to manipulate meningeal lymphatic function.

In the current study, the authors observed that meningeal lymphangiogenesis and increased lymphatic drainage occurred from days 10 to 14 and persisted until at least day 60 after ICH. Second, impairment of meningeal lymphatic function in ICH animals impeded intraparenchymal hematoma resolution, whereas its enhancement reduced hematoma volume. Third, pharmacologically targeting the meningeal lymphatic system by cilostazol effectively promoted meningeal lymphatic function and subsequently increased RBC uptake and drainage. Last, early enhancement of meningeal lymphatic function accelerated hematoma resolution and ameliorated neurological deficits, iron burden, neuron loss, and astrogliosis. These observations are consistent with previous studies that augmentation of meningeal lymphatic function alleviates neuroinflammation, brain damage, and neurological implications in CNS diseases.

While it remains unclear how a CSF drainage system within the dura matter affects hematoma removal in the brain parenchyma, one interpretation of these data could be that a lack of meningeal lymphatic vessels compromises outflow of interstitial macromolecules through the glymphatic system, a paravascular route penetrating brain tissues and drains macromolecules from the brain parenchyma. Understanding the interplay between these 2 brain drainage systems in mediating intraparenchymal hematoma clearance after ICH is likely to increase the scope of clinical application targeting these systems.

6 figures with histology

5. Kumaria A, Gruener AM, Dow GR, et al. An explanation for Terson syndrome at last: the glymphatic reflux theory. J Neurol 2022;269:1264–71. Available from: https://doi.org/10.1007/s00415-021-10686-4

Terson Syndrome (TS) describes the presence of intraocular hemorrhage in patients with intracranial hemorrhage, typically subarachnoid hemorrhage. Despite TS being a well-defined and frequently occurring phenomenon, its pathophysiology remains controversial. This review presents the current understanding of TS, describing a contemporary and more plausible pathomechanism of TS, given recent advances in ophthalmic science and neurobiology. Previously proposed theories included a sudden rise in intracranial pressure (ICP) transmitted to the optic nerve sheath leading to rupture of retinal vessels; or intracranial blood extending to the orbit via the optic nerve sheath. The origin of blood in TS is uncertain, but retinal vessels appear to be an unlikely source. In addition, an anatomical pathway for blood to enter the eye from the intracranial space remains poorly defined. An ocular glymphatic system has recently been described, drainage of which from the globe into intracranial glymphatics is reliant on the pressure gradient between intraocular pressure and intracranial pressure.

In cadaveric studies, post-mortem instillation of India ink in subarachnoid spaces remote to the optic system resulted in accumulation in perivascular spaces, including those of the optic nerve. A CSF-instilled, CSF-based contrast agent was found to diffuse freely through extravascular channels through the optic nerve across glymphatic pathways as seen on MRI in human subjects. This adds weight to animal studies that have previously demonstrated continuity between ocular glymphatics at the ocular lamina cribrosa and CSF cisterns.

The glymphatic pathway is the only extravascular anatomical conduit between the subarachnoid space and the retina. The authors propose that subarachnoid blood in skull base cisterns near the optic nerve is the substrate of blood in TS. Raised ICP causes it to be refluxed through glymphatic channels into the globe, resulting in intraocular hemorrhage. The authors present glymphatic reflux as an alternative theory to explain the phenomenon of Terson Syndrome.

2 figures with eye fundus photographs

6. Sharobeam A, Yan B. Advanced imaging in acute ischemic stroke: an updated guide to the hub-and-spoke hospitals. Curr Opin Neurol 2022;35:24–30

The hub-and-spoke model refers to a model of service provision in which a primary ‘hub’ hospital provides a full suite of stroke intervention services and secondary ‘spoke’ hospitals provide more limited stroke services. Secondary ‘spoke’ hospitals can transfer patients needing more specialized services to the hub for treatment. In AIS, patients may present to a spoke hospital first, undergo brain imaging and receive thrombolytic therapy. If deemed suitable, these patients will then be transferred to hub for further management with EVT or other treatments, such as hemicraniectomy. Otherwise, these patients will remain at the spoke hospital for standard stroke care. The hub hospital provides a full suite of specialist stroke services. This includes healthcare personnel with specific expertise in several disciplines, including vascular neurology and neurosurgery; advanced neuroimaging capabilities such as MRI and catheter based cerebral angiography; carotid endarterectomy, and endovascular thrombectomy; and other specific infrastructures such as an intensive care unit and participation in a stroke registry.

Spoke hospitals have the capacity to provide initial management for patients with ischemic stroke. Typically, this includes the ability to perform basic stroke imaging with CT brain, CT angiography and the ability to provide thrombolytic therapy. The spoke hospital may also have other services available, including advanced imaging, a stroke unit and intensive care services. Spoke hospitals are typically primary stroke centers (PSC) in metropolitan hospitals or in regional areas, acute stroke ready hospitals (ASRH). To be designated as such, acute stroke ready hospitals at a minimum need to provide thrombolysis and clinicians who are experienced in acute stroke care.

1 figure, no imaging

7. Geitenbeek RTJ, Martin E, Graven LH, et al. Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients. J Neurooncol 2022;156:559–67. Available from: https://doi.org/10.1007/s11060-021-03936-y

MPNSTs are aggressive soft tissue sarcomas (STS), accounting for 2–3% of all STS. Although MPNSTs are rare in the common population, NF1 patients have an 8–13% lifetime risk of developing an MPNST. MPNSTs generally have poor clinical outcomes, being the leading cause of mortality in NF1 patients. The median survival of localized disease ranges from 5–6 years, demanding aggressive treatment. Surgical resection is the only curative therapeutic option improving survival as MPNSTs respond poorly to chemo- and radiotherapy. While the resection of MPNSTs commonly results in high postoperative morbidity and motor deficits, BPNSTs may be removed by intracapsular resections, minimizing neurologic damage.

18F-FDG PET-CT, using standardized uptake values (SUVs) and tumor-to-liver ratios as semi-quantitative metabolic imaging markers, has been increasingly used as a non-invasive diagnostic tool for the characterization of PNSTs in NF1 patients. However, ideal parameters and their corresponding thresholds have yet to be elucidated. There is large variation in current literature regarding this matter, part of which might be caused by variation among scanners and scanning protocols. Suggested optimal threshold values of semi-quantitative parameters vary greatly, but the SUVmax threshold of ≥ 3.5 is commonly cited. However, its value has been doubted since it may provide high false positive rates.

FDG PET-CT has been shown helpful, but ideal threshold values of semi-quantitative markers remain unclear, partially because of variation among scanners. Using EU-certified scanners diagnostic accuracy of ideal and commonly used 18F-FDG PET-CT thresholds were investigated and differences between adult and pediatric lesions were evaluated.

Sixty patients were included (10 MPNSTs). Ideal threshold values were 5.8 for SUVmax (sensitivity 0.70, specificity 0.92), 5.0 for SUVpeak (sensitivity 0.70, specificity 0.97), 1.7 for  Tumor-to-liver- TLmax (sensitivity 0.90, specificity 0.86), and 2.3 for TLmean (sensitivity 0.90, specificity 0.79). The standard TLmean threshold value of 2.0 yielded a sensitivity of 0.90 and specificity of 0.74, while the standard SUVmax threshold value of 3.5 yielded a sensitivity of 0.80 and specificity of 0.63. SUVmax and adjusted SUV for lean body mass (SUL) were lower in children, but tumor-to-liver ratios were similar in adult and pediatric lesions. Using TLmean > 2.0 or TLmean < 2.0 and SUVmax > 3.5, a sensitivity and specificity of 1.00 and 0.63 can be achieved.

18F-FDG PET-CT offers adequate accuracy to detect MPNSTs. SUV values in pediatric MPNSTs may be lower, but tumor-to-liver ratios are not. By combining TLmean and SUVmax values, a 100% sensitivity can be achieved with acceptable specificity.

2 figures, 3 tables

8. Tateshima S, Saber H, Colby GP, et al. Robotic assistant spinal angiography: a case report and technical considerations. BMJ Case Rep 2021;14:1–3

This is the first report of in-human clinical use of robotic assistance for spinal angiography. While the Corindus robot is designed for coronary and peripheral vascular procedures, the authors summarized their initial experience including the technical advantages and challenges to perform robotic spinal angiography. The catheter was primarily manipulated using a push–pull and rotation joystick control solely based on the visual information. Particular attention was given to the deflection of the catheter tip in lieu of haptic feedback. Also, they developed the wire-aid guidance (WAG) technique instead of using a short puff of contrast media to confirm the successful catheterization to a segment artery. The WAG technique uses a soft micro guidewire to be pushed out of the catheter when the interventionalist thinks the catheter tip has engaged a segmental artery. If the catheter tip successfully engages a segmental artery, the guidewire travels straight into it. If not, the guidewire wags downwards or upwards and runs along the wall of the aorta. Given the current workflow using the robotic system, the WAG technique makes the overall procedure easier and faster than the established contrast-injection method. It can also further reduce overall contrast load given to the patient. The challenges include lack of haptic feedback, the learning curve and time required to adjust to new system, and the short working length or short range of the robotic arm motion which currently is 20 cm. (Ideally it should be around 40 cm.)

4 figures

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