De novo variants in RNF213 are associated with a clinical spectrum ranging from Leigh syndrome to early-onset stroke.

PURPOSE: RNF213, encoding a giant E3 ubiquitin ligase, has been recognized for its role as a key susceptibility gene for moyamoya disease. Case reports have also implicated specific variants in RNF213 with an early-onset form of moyamoya disease with full penetrance. We aimed to expand the phenotypic spectrum of monogenic RNF213-related disease and to evaluate genotype-phenotype correlations. METHODS: Patients were identified through reanalysis of exome sequencing data of an unselected cohort of unsolved pediatric cases and through GeneMatcher or ClinVar. Functional characterization was done by proteomics analysis and oxidative phosphorylation enzyme activities using patient-derived fibroblasts. RESULTS: We identified 14 individuals from 13 unrelated families with (de novo) missense variants in RNF213 clustering within or around the Really Interesting New Gene (RING) domain. Individuals presented either with early-onset stroke (n = 11) or with Leigh syndrome (n = 3). No genotype-phenotype correlation could be established. Proteomics using patient-derived fibroblasts revealed no significant differences between clinical subgroups. 3D modeling revealed a clustering of missense variants in the tertiary structure of RNF213 potentially affecting zinc-binding suggesting a gain-of-function or dominant negative effect. CONCLUSION: De novo missense variants in RNF213 clustering in the E3 RING or other regions affecting zinc-binding lead to an early-onset syndrome characterized by stroke or Leigh syndrome.

Flow control in the middle cerebral artery during thrombectomy: the effect of anatomy, catheter size and tip location.

BACKGROUND: Catheter size, location and circle of Willis anatomy impact the flow conditions during interventional stroke therapy. The aim of the study was to systematically investigate the influence of these factors on flow control in the middle cerebral artery by means of a computational model based on 100 patients with stroke who received endovascular treatment. METHODS: The dimensions of the cervical and intracranial cerebral arteries of 100 patients who received endovascular mechanical thrombectomy for acute ischemic stroke were measured and a three-dimensional model of the circle of Willis was created based on these data. Flow control in the middle cerebral artery with variations in catheter size, catheter location and configurations of collateral vessels was determined using a computational model. A total of 48 scenarios were analyzed. RESULTS: Flow reversal with a distal aspiration catheter alone was not possible in the internal carotid artery and only sometimes possible in the middle cerebral artery (14 of 48 cases). The Catalyst 7 catheter was more often successful in achieving flow reversal than Catalyst 5 or 6 catheters (p<0.001). In a full circle of Willis anatomy, flow reversal was almost never possible. The absence of one or more communicating arteries significantly influenced flow direction compared with the full anatomy with all communicating arteries present (p=0.028). CONCLUSION: Choosing the biggest possible aspiration catheter and locating it in the middle cerebral artery significantly increases the chances of successful flow control. Flow through the collaterals may impair the flow, and circle of Willis anatomy should be considered during aspiration thrombectomy.

Ocular Trauma with Ophthalmic Artery Injury as a Rare Cause of Subarachnoid Hemorrhage: a Case Report and Review of the Literature.

BACKGROUND AND IMPORTANCE: Traumatic avulsion of the ophthalmic artery is a rare cause of subarachnoid hemorrhage (SAH). In this case, a relative minor fall with isolated ocular trauma caused bulbar dislocation and rupture of the ophthalmic artery in its intracranial segment resulting in subarachnoid bleeding. CLINICAL PRESENTATION: In a female patient in her 70s, a direct penetrating trauma to the orbit by a door handle resulted in basal SAH with blood dispersion into both Sylvian fissures. Cerebral angiography revealed a blunt-ending stump at the origin of the ophthalmic artery. To provide protection against further bleeding, a flow diverter stent was placed in the internal carotid artery to cover the origin of the ophthalmic artery. After a longer intensive care stay complicated by pneumonia and respiratory insufficiency, the patient made a full recovery. Of all four reported cases (including ours), delayed cerebral ischemia was seen in one patient and hydrocephalus in two patients. These potential complications necessitate close observation and fitting treatment similar to aneurysmal SAH. CONCLUSION: Due to similar physiologic aspects, this type of bleed mimics many aspects of aneurysmal SAH. In this case, we observed no hydrocephalus or the development of delayed cerebral ischemia. This represents, however, the first reported case treated by placement of a flow diverter stent to prevent rebleeding and pseudoaneurysm formation.

Anti-SEZ6L2 antibodies in paraneoplastic cerebellar syndrome: case report and review of the literature.

Seizure Related 6 Homolog Like 2 (SEZ6L2) protein has been shown to have implications in neuronal and especially motor function development. In oncology, overexpression of SEZ6L2 serves as a negative prognostic marker in several tumor entities. Recently, few cases of anti-SEZ6L2 antibody mediated cerebellar syndromes were reported. In this article, we present a case of a 70-year-old woman with subacute onset of gait disturbance, dysarthria and limb ataxia. Serum anti-SEZ6L2 antibodies were markedly increased, and further diagnostic workup revealed left sided breast cancer. Neurological symptoms and SEZ6L2 titer significantly improved after curative tumor therapy. This is a very rare and educationally important report of anti-SEZ6L2 autoimmune cerebellar syndrome with a paraneoplastic etiology. Additionally, we performed a review of the current literature for SEZ6L2, focusing on comparing the published cases on autoimmune cerebellar syndrome.

Interventional embolization combined with surgical resection for treatment of extracranial AVM of the head and neck: A monocentric retrospective analysis.

OBJECTIVES: The aim of this study was to demonstrate the efficacy and feasibility of treating patients with extracranial arteriovenous malformations (AVM) of the head and neck with interventional embolization followed by surgical resection. METHODS: We reviewed the charts of all patients between 2012 and 2021 with extracranial AVM of the head and neck scheduled for interdisciplinary treatment according to University Hospital RWTH Aachen's protocol and conducted standardized interviews using a newly developed questionnaire. Interview results, as well as clinical examination and radiographic outcome results were analyzed to help determine the efficacy of our treatment approach. RESULTS: We included 10 patients (8 female, 2 male), with a mean age of 33.5 (11-61) years who were scheduled for treatment of the AVM with interventional embolization followed by surgical resection. In 6 of the 10 patients (60%) the lesion was located in extracranial soft tissue only. In one patient (10%), the lesion was located in bone tissue only. A combined intraosseous and oral soft tissue lesion was seen in the remaining 3 patients (30%). Radiographic resolution was achieved in 62.5% of cases and a significant decrease of symptoms was identified (p = 0.002). None of the patients reported dissatisfaction and no major complications occurred. CONCLUSION: An interdisciplinary treatment approach combining neuroradiological interventions with surgical resection appears to be an effective treatment with an acceptable complication rate. Patients treated according to our protocol showed a high satisfaction rate, regardless of the radiographic outcome. Standardized follow-up allows for early detection of recurrences and helps with subjective patient satisfaction.

MRI appearance of chronic subdural hematoma.

Objective: We aimed to describe the magnetic resonance imaging (MRI) characteristics of chronic subdural hematoma (cSDH) and to ascribe MRI patterns. Methods: A total of 20 patients having 27 subdural hematomas underwent contrast-enhanced (CE) MRI of the brain at our institution between April 2019 and May 2021. The images were independently evaluated by two experienced neuroradiologists with regard to imaging characteristics on T1w, T2w, T2*-GRE, FLAIR, diffusion-weighted magnetic resonance imaging (DWI), and CE images. Results: The signal characteristics of cSDH on T1- and T2-weighted images were rather heterogeneous. The majority of hematomas (74%) had internal septations. Surprisingly, contrast enhancement along the outer membrane adjacent to the cranium was noticed in all hematomas. There was also contrast enhancement along the inner membrane adjacent to the brain in more than one-third of the hematomas (37%). In approximately two-thirds of the cSDH (62%), there was a mass-like enhancement of the hematoma. Most hematomas (89%) were partially hypointense on T2*-GRE and/or susceptibility-weighted imaging (SWI). Restricted diffusion was detected in approximately one-third of the hematomas (33%). Conclusion: Consistent contrast enhancement along the outer membrane, triangular-shaped contrast enhancement at the borders of the cSDH, and infrequent enhancement of the inner membrane may help to distinguish cSDH from other entities such as empyema and tumors. Mass-like enhancement may refer to non-solid hematomas and could be an indicator for hematoma growth and a possible surrogate for successful endovascular embolization. Restricted diffusion in a subdural mass is not specific for empyema but may also be found in cSDH.

Interventional therapy of extracranial arteriovenous malformations of the head and neck-A systematic review.

OBJECTIVES: The primary aim of this study was to conduct a meta-analysis of the literature on interventional treatment for patients with extracranial AVM of the head and neck to identify a superior treatment. The secondary aim was to evaluate the methodological quality of associated articles published between 2000-2020. METHODS: The literature search was conducted on PubMed, Embase, the Cochrane Library, and scholar.google.com. Studies, meeting the acceptable reference standard underwent meta-analysis. All identified literature underwent methodological quality analysis. RESULTS: Of 1560 screened articles, 56 were included in the literature review. Appropriate diagnostic tests were reported in 98% of included articles. 13% of included articles did not specify the embolization agent. Outcome analysis varied throughout. 45% of the authors used radiographic imaging for follow-up. 77% specified the span of follow-up of their entire patient collective. Two articles met the inclusion criteria for meta-analysis. Curing rate of transarterial ethanol embolization for intraosseous AVM was 83% with a complication rate of 58%. Curing rate of ethanol combined with NBCA or Onyx in soft tissue AVM was 18% with a complication rate of 87%. CONCLUSION: Our literature review revealed an absence of treatment or reporting standards for extracranial AVM of the head and neck. The meta-analysis is comprised of two articles and methodological quality is heterogeneous. We recommend implementing consistent reporting standards to facilitate comparability of studies and to provide robust data for the development of an evidence-based treatment strategy. ADVANCES IN KNOWLEDGE: Meta-analysis showed a favorable radiological outcome for intraosseous AVM when treated with intraarterial ethanol embolization. Our analysis demonstrated that the published data on extracranial AVMs of the head and neck is lacking in consistency and quality, prompting agreement for the need of standardized reporting on AVM treatments.

Extending stroke CT angiography to the full chest allows for detection of additional pulmonary opacifications in acute stroke patients.

BACKGROUND AND PURPOSE: During epidemics with an increased prevalence of pulmonary infections, extending stroke CTA examinations of acute stroke workup to the whole chest may allow for the identification of pulmonary findings that would have been missed on standard CTA examinations. MATERIALS AND METHODS: Our analysis comprised 216 patients with suspicion of stroke who received extended full-chest cerebrovascular CTA examinations from January 27th 2020 - date of the first confirmed Covid-19 case in Germany - until April 30th 2020. RESULTS: Consolidations and ground-glass opacifications were found in 73 of all 216 patients (34%). Opacifications were found in the upper chest in 51/216 patients (23%). There were lower-chest opacifications in 22 of 165 patients (13%) with unsuspicious upper-chest scans. In these 22 patients, there were consolidations in 10 cases (45%), ground-glass opacifications in 10 cases (45%), and both in 2 cases (10%). CONCLUSIONS: Our study showed that extending the scan volume of an emergency stroke CTA to the whole chest reveals a considerable number of opacifications that would have been missed on a standard CTA. Even though these findings were rarely indicative of COVID-19, a large number of opacifications warranted further investigation.

Clinical Outcome and Prognostic Factors of Patients with Perimesencephalic and Nonperimesencephalic Subarachnoid Hemorrhage.

OBJECTIVE: To demonstrate the clinical outcome of patients with nonperimesencephalic subarachnoid hemorrhage (npSAH) compared with patients with aneurysmal SAH (aSAH) and perimesencephalic SAH (pSAH) and to evaluate predictive value of various clinical and radiological findings in patients with npSAH. METHODS: We retrospectively identified patients with SAH who presented at our institution between 2009 and 2018. We analyzed demographic and clinical data and outcomes. Multivariable analysis was performed for outcome parameters. RESULTS: Of 608 patients with confirmed SAH, 78% had aSAH, and 22% had nonaneurysmal SAH. Nonaneurysmal SAH was perimesencephalic in 30% of cases and nonperimesencephalic in 70%. Initial clinical status (Hunt and Hess score) was significantly worse in patients with aSAH compared with patients with nonaneurysmal SAH. Complications such as delayed cerebral ischemia occurred significantly more often in patients with aSAH. Patients with pSAH had a more favorable clinical course than patients with aSAH or npSAH. There was no significant difference in 30-day mortality between aSAH (29%) and npSAH (28%) patients (P = 0.835). Hunt and Hess score emerged as a strong predictor of unfavorable outcome in both aSAH and npSAH in multivariable regression. CONCLUSIONS: Patients with npSAH had a similar clinical outcome as patients with aSAH, although there were significantly fewer clinical complications in patients with npSAH. Patients with pSAH demonstrated an overall good clinical course. Our multivariable analysis showed that initial Hunt and Hess score was an important predictor for clinical outcome in aSAH as well as npSAH.

Seeing the good in the bad: actual clinical outcome of thrombectomy stroke patients with formally unfavorable outcome.

PURPOSE: Clinical outcome of stroke patients is usually classified into favorable (modified Rankin scale (mRS) 0-2) and unfavorable (mRS 3-5) outcome according to the modified Rankin scale. We took a closer look at the clinical course of thrombectomy stroke patients with formal unfavorable outcome and assessed whether we could achieve our treatment goals and/or neurological improvement in these patients. METHODS: We studied 107 patients with occlusions in the terminal carotid artery or the M1 segment of the middle cerebral artery, in whom complete recanalization (eTICI 3) could be achieved, and who had an mRS of 3-5 at 90 days. We analyzed whether an individual treatment goal (i.e., preventing aphasia) and neurological improvement (NIHSS) could be achieved. In addition, we examined whether there was clinical improvement on the mRS. RESULTS: The treatment goal was achieved in 52% (53/103) and neurological improvement in 65% (67/103). mRS 90 days post-stroke was better than mRS upon admission in 36% (38/107) and better than or equal to mRS upon admission in 80% (86/107). Of the 93 patients with known pre-stroke mRS, 18% (17/93) already had an mRS ≥ 3, with 15 of these 17 patients having a worse mRS on admission than before. Of these 17 patients, 18% regained baseline, and 24% improved from admission. CONCLUSION: Dichotomizing the mRS into favorable and unfavorable outcome does not do justice to the full spectrum of stroke. Patients with formal unfavorable outcome after mRS can improve neurologically, achieve treatment goals, and even regain their admission or pre-stroke mRS.

Is the detectability of the spot sign on CT angiography depending on slice thickness and reconstruction type?

OBJECTIVE: The spot sign is a validated imaging marker widely used in CT angiography (CTA) to detect active bleeding and a higher risk of hematoma expansion in patients with intracerebral hemorrhage (ICH). The aim of this study was to investigate the detectability of spot signs on thin multiplanar projection reconstruction (MPR) images compared to thicker maximum intensity projection (MIP) images. METHODS: In this retrospective analysis, we assessed imaging data of 146 patients with primary hypertensive/microangiopathic ICH who received emergency non-contrast computed tomography (NCCT) and CTA. Two experienced radiologists, blinded to each other, evaluated images of thin (1 mm) MPR images and thick (3 mm) MIP images on the presence of spot signs and performed a consensus reading. Kappa tests were used for data comparison. RESULTS: In total, spot signs were observed in 27 cases (=18.5 %) in both thin MPR and thick MIP slices. Detectability of the spot sign did not differ in 1 mm MPR images and 3 mm MIP images (Cohen's kappa, 1.0; p = 0.00). Also, when the readings of the two radiologists were analyzed separately, results for MPR and MIP slices were similar (MPR: Cohen's kappa, 0.81, p = 0.00; MIP: Cohen's kappa, 0.74; p = 0.00). CONCLUSION: No significant difference in the detectability of the spot sign could be demonstrated when comparing 1 mm MPR images with 3 mm MIP images.