Endovascular treatment of distal anterior cerebral artery aneurysms using flow modulation devices: mid- and long-term results from a two-center study.

Purpose: Flow-diverter (FD) stents have become an established treatment for intracranial aneurysms in recent years, but their use for aneurysms in distal cerebral vessels with small carrier vessel diameters remains controversial. This study describes the method and mid- and long-term outcomes of FD treatment of distal anterior cerebral artery aneurysms (DACAAs) at two neurointerventional centers, to elucidate this topic and provide more in-depth data. Methods: Data for all patients at two neurointerventional centers who were treated with FDs for DACAAs in the pericallosal and supracallosal segment of the anterior cerebral artery were retrospectively analyzed. Data on periprocedural complications, and short-, mid- and long-term follow-up findings were recorded. Results: Forty-one patients were eligible for inclusion in the study. Three FD models were used, one of which had an anti-thrombotic coating. Two periprocedural complications (5%) occurred but did not cause a change in the mRS. In the long-term follow-up, at 29 months and beyond, 83% of assessable patients showed complete occlusion of the aneurysms without new neurological deficits. Conclusion: FDs are a safe and effective treatment approach for DACAAs. This study indicated a low risk of complications, and high closure rates in short-, mid- and long-term follow-up.

Triple platelet inhibition in intracranial thrombectomy with additional acute cervical stent angioplasty due to tandem lesion: a retrospective single-center analysis.

BACKGROUND: Acute stroke treatment with intracranial thrombectomy and treatment of ipsilateral carotid artery stenosis/occlusion ("tandem lesion", TL) in one session is considered safe. However, the risk of stent restenosis after TL treatment is high, and antiplatelet therapy (APT) preventing restenosis must be well balanced to avoid intracranial hemorrhage. We investigated the safety and 90-day outcome of patients receiving TL treatment under triple-APT, focused on stent-patency and possible disadvantageous comorbidities. METHODS: Patients receiving TL treatment in the setting of acute stroke between 2013 and 2022 were analyzed regarding peri-/postprocedural safety and stent patency after 90 days. All patients received intravenous eptifibatide and acetylsalicylic acid and one of the three drugs prasugrel, clopidogrel, or ticagrelor. Duplex imaging was performed 24 h after treatment, at discharge and 90 days, and digital subtraction angiography was performed if restenosis was suspected. RESULTS: 176 patients were included. Periprocedural complications occurred in 2.3% of the patients at no periprocedural death, and in-hospital death in 13.6%. Discharge mRS score was maintained or improved at the 90-day follow-up in 86%, 4.54% had an in-stent restenosis requiring treatment at 90 days. No recorded comorbidity considered disadvantageous for stent patency showed statistical significance, the duration of the endovascular procedure had no significant effect on outcome. CONCLUSION: In our data, TL treatment with triple APT resulted in a low restenosis rate, low rates of sICH and a comparably high number of patients with favorable outcome. Aggressive APT in the initial phase may therefore have the potential to prevent recurrent stroke better than restrained platelet inhibition. Comorbidities did not influence stent patency.

High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial.

BACKGROUND: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL. METHODS: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete. FINDINGS: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications. INTERPRETATION: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials. FUNDING: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg.

Drug-Coated Balloons for Treatment of Internal Carotid Artery Restenosis After Stenting: A Single-Center Mid-Term Outcome Study.

PURPOSE: Endovascular and surgical treatments of stenosis of the extracranial internal carotid artery (ICA) are common procedures, yet both introduce a risk of restenosis due to endothelial hyperplasia. Drug-coated balloons (DCBs) are designed to decrease neointimal hyperplasia, however rarely used in the neurovascular setting. This study retrospectively analyzes mid-term results of DCB-treated in-stent restenosis (ISR) of the ICA. MATERIALS AND METHODS: The medical history, comorbidities, and periprocedural data of patients receiving DCB treatment for > 50% ISR of the ICA after carotid artery stenting were analyzed. Follow-up after DCB treatment was performed with Doppler ultrasound. Suspicious cases were checked with CT- or MR-angiography and-if there was agreement between the modalities-validated with digital subtraction angiography. Potential risk factors for restenosis and differences in outcomes after PTA with three types of DCB balloons were evaluated. RESULTS: DCB treatment was performed in 109 cases, 0.9% of which involved in-hospital major stroke; no minor strokes occurred. A total of 17 patients (15.6%) had recurrent ISR after DCB treatment, after a mean time of 30.2 months (7-85 months). Tobacco use was significantly associated with a higher incidence of recurrent ISR. CONCLUSION: DCB angioplasty for ISR is an effective treatment that may delay and decrease restenosis. Treating comorbidities and adopting lifestyle changes may additionally help prevent ISR.

Is Crash Loading Acceptable in Carotid Artery Stenting? : Results of Antiplatelet Crash Loading vs. Semi-crash vs. Elective Loading in a Large Study Population.

PURPOSE: In elective carotid artery stenting (CAS), antiplatelet therapy (APT) is crucial. Several international societies have provided guidelines for loading time and dosage in endovascular treatment; however, no recommendations have been made for urgent, nonthrombectomy-associated CAS without adequate loading time. Here, we investigated the short-term outcomes for APT-naïve patients receiving "crash loading" (CL) on the day of intervention, compared with those for patients wi APT onset 3-5 days (semi-CL) or more than 5 days before CAS (EL). METHODS: Outcomes of patients 30 days after CAS were evaluated in terms of the rates of in-stent thrombus, re-stenosis, stroke, hemorrhagic and thrombotic events, other periprocedural occurrences, in-hospital death and CAS-associated death. Patients' biological, pathological and hemostatic factors were recorded and compared. RESULTS: A total of 1158 patients who received CAS at the authors' neuroradiology institution were analyzed: 275 EL, 846 semi-CL, and 37 CL. The patients receiving CL had the lowest rate of stroke, but the highest rates of CAS-associated and in-hospital deaths, although the deaths were not necessarily associated with APT. In-stent thrombosis was the highest in the semi-CL group. The rates and types of periprocedural occurrences favored the CL group. CONCLUSION: With the medical regimen used in this study, urgent CAS with CL APT did not produce more ischemic, thrombotic and hemorrhagic complications than longer loading times. However, careful patient selection might be crucial and adequate loading times should remain the standard of care.

Target insertion depth of nasopharyngeal temperature probes in children: A prospective observational study analyzing magnetic resonance images.

BACKGROUND: Core temperature monitoring is indispensable to prevent children from perioperative thermal perturbations. Although nasopharyngeal measurements are commonly used in anesthesia and considered to reflect core temperature accurately, standardized target depths for probe insertion are unknown in children. AIMS: Our primary goal was to determine a target depth of nasopharyngeal temperature probe insertion in children by measuring distances on magnetic resonance imaging (MRI). Secondary aims were to correlate these measurements with biometric variables and facial landmark-distances to derive formulas estimating target depth. METHODS: We conducted a prospective observational study in children ≤12 years undergoing cranial MRI with anesthesia. We documented patient characteristics and measured the landmark-distances nostril-mandible, nostril-tragus, and philtrum-tragus on patient's faces. On MRI, the target point for the probe tip was considered to be the site of the nasopharyngeal mucosa with the closest proximity to the internal carotid artery. After its determination in the transverse axis and triangulation to the sagittal axis, we measured the distance to the nostril. This distance, defined as target insertion depth, was correlated with the patient characteristics and used for univariate and multiple linear regression analysis. RESULTS: One hundred twenty children with a mean age of 4.5 years were included. The target insertion depth ranged from 61.8 mm in infants to 89.8 mm in 12-year-old children. Height correlated best (ρ = 0.685, 95%-CI: [0.57-0.77]). The best-fit estimation in millimeters, "40.8 + height [cm] × 0.32,″ would lead to a placement in the target position in 67% of cases. A simplified approach by categories of 50-80, 80-110, 110-130, and >130 cm height with target insertion depths of 60, 70, 80, and 85 mm, respectively, achieved similar probabilities. CONCLUSIONS: Height-based formulas could be a valuable proxy for the insertion depth of nasopharyngeal temperature probes. Further clinical trials are necessary to investigate their measurement accuracy.

Carotid Artery Stenting in Patients with Symptomatic and Asymptomatic Stenosis: In-Hospital Clinical Outcomes at a Single Neurovascular Center.

BACKGROUND: Carotid artery stenting (CAS) is a minimally invasive and proven percutaneous procedure that is widely used to treat patients with symptomatic and asymptomatic carotid artery stenosis. The purpose of this study was to characterize the in-hospital outcomes of symptomatic and asymptomatic patients undergoing CAS at a single neurovascular center. METHODS: The study was conducted as a retrospective analysis of 1158 patients (asymptomatic, n = 636; symptomatic, n = 522; male, n = 816; median age, 71 years; NASCET method, 70-99% stenosis, n = 830) who underwent CAS between May 2009 and December 2020. In-hospital neurological outcomes, adverse reactions to iodinated contrast media, acute myocardial infarction, intraprocedural complications, and access-site issues were evaluated. The primary endpoints were disabling stroke (including disabling cerebral hyperperfusion syndrome [CHS]) and all in-hospital deaths. RESULTS: A carotid stent could not be deployed in one patient due to calcified plaques (technical failure rate of 0.09%). Four patients (0.3%) experienced in-hospital, stroke-associated death, while five patients (0.4%) died from non-stroke-related causes. All stroke-associated deaths occurred in the symptomatic group and were due to CHS. The disabling stroke rate was 0.9% overall (n = 10; 0.5% versus 1.3% in asymptomatic versus symptomatic patients, respectively). Nineteen patients (1.6%) reached the in-hospital primary endpoint. More patients in the symptomatic group achieved this endpoint than in the asymptomatic group (2.5% versus 0.9%, respectively; p = 0.060). CONCLUSIONS: An evaluation was conducted on the in-hospital outcomes of 1158 patients at a single center who underwent CAS and was performed by trained physicians who were supervised by a senior neurovascular interventionist with over 20 years of experience, confirming the excellent safety profile of this procedure with a low rate of complications.

Combined Anticoagulation and Antiaggregation in Acute Cervical Artery Dissection.

Cervical artery dissection (CAD) is a frequent cause of stroke in young adults. Previous studies investigating the efficiency of anticoagulation (AC) versus antiplatelet therapy (AT) found an insignificant difference. We therefore retrospectively evaluated a combination of AC plus AT in patients with acute CAD regarding safety and efficacy. Twenty-eight patients with CAD and minor neurological symptoms/no major infarction received either single (n = 14) or dual AT (n = 14) combined with AC. Angiographic follow-up during hospitalization, 4-8 weeks and 3-6 months after CAD focused on occlusion, residual stenosis, and functional recanalization. Possible adverse events were surveyed. We compared the AC plus AT group to 22 patients with acute CAD treated with AC or AT. Compared to preceding AC-/AT-only studies, AC plus single or dual AT resulted in more frequent, faster recanalization. Frequency and severity of adverse events was comparable. No major adverse events or death occurred. Preceding works on conservative treatment of CAD are discussed and compared to this study. Considerations are given to pathophysiology and the dynamic of CAD. Combining AC plus AT in CAD may result in more reliable recanalization in a shorter time. The risk for adverse events appears similar to treatment with only AC or AT.

Working with estimation-formulas to predict nasopharyngeal airway insertion depth in children: Looking at magnetic resonance images - A prospective observational study (WEND:LI-Study).

OBJECTIVE: To determine the accuracy of the recently proposed landmark-method 'nostril-to-tragus minus 10 mm' and compare with ERC-recommended distances for nasopharyngeal airway length sizing in children. METHOD: We conducted a prospective observational study in sedated children < 12 years. Nasopharyngeal airways were inserted following 'nostril-to-tragus minus 10 mm'. Primary outcome was the rate of nasopharyngeal airway tips between soft palate and epiglottis on magnetic resonance imaging (MRI) indicated for medical reasons. An optimal placement was defined when the tip lied within 25-75% of the total soft palate-to-epiglottis distance. Between 0-100% of this distance, placement was still considered acceptable, below 0% too proximal or above 100% too distal. Secondary outcomes were the rate of adverse events, the qualitative positions of airway tips, and the comparison of ́nostril-to-tragus minus 10 mm with the ERC-recommended distances 'nostril-to-angle of the mandible' and 'nostril-to-tragus' with objective MRI measurements. RESULTS: We analysed 92 patients with a mean age of 4.3 years. Nasopharyngeal airways were optimally placed in 37.0% (8.7% too proximal-77.2% acceptable-14.1% too distal). Three qualitative malpositions, but no airway-associated adverse event occurred. Objective measurements on MRI revealed the probability of 40.2% optimally placed nasopharyngeal airways (5.4%-67.4%-27.2%) for 'nostril-to-tragus minus 10 mm', 38.0% (17.4%-58.7%-23.9%) for 'nostril-to-mandible' and 13.0% (0%-28.3%-71.7%) for 'nostril-to-tragus', respectively. CONCLUSION: No landmark-method predicted nasopharyngeal airway position reliably. 'Nostril-to-tragus minus 10 mm' seems the least inaccurate one and could be a valuable approximation until another estimation-formula proves more accurate. During insertion, careful clinical evaluation of airway patency is crucial. REGISTERED CLINICAL TRIAL: German Clinical Trials Register; DRKS00021007.

Case Report: Findings Suggestive of Paraclinical Progressive Multifocal Leukoencephalopathy and Lung Cancer-Derived Brain Metastases in an MS Patient Treated With Fingolimod.

Fingolimod represents a highly effective disease-modifying drug in patients with active relapsing-remitting multiple sclerosis (RRMS). Its immunosuppressive effects can mediate adverse events like increased risk of cancer development or appearance of opportunistic infections. Progressive multifocal leukoencephalopathy (PML)-representing a severe opportunistic infection-has been only infrequently described during Fingolimod treatment. Here, we present a case of a 63-year-old women with pre-diagnosed RRMS who presented with new multiple cerebral lesions in a routine MRI scan, also including a tumefactive lesion in the left parietal lobe, eventually leading to the diagnosis of brain metastases derived by an adenocarcinoma of the lung. Additionally, a JCV-DNA-PCR in the cerebrospinal fluid revealed positive results, corresponding to a paraclinical progressive multifocal leukoencephalopathy. In conclusion, adverse events potentially associated with immunosuppression can occur during Fingolimod treatment. In this context, the occurrence of cancer and opportunistic infections should be carefully monitored. Here, we report a case in which JCV-DNA-PCR in the cerebrospinal fluid suggests asymptomatic PML and simultaneously lung cancer brain metastases developed. While it is rather unlikely that either event occurred as an adverse event of fingolimod treatment, a contributing effect cannot be formally excluded.

KCNA2 Autoimmunity in Progressive Cognitive Impairment: Case Series and Literature Review.

Autoimmune dementia is a novel and expanding field which subsumes neuropsychiatric disorders with predominant cognitive impairments due to an underlying autoimmune etiology. Progressive dementias with atypical clinical presentation should trigger a thorough diagnostic approach including testing for neural surface and intracellular antibodies to avoid a delay in accurate diagnosis and initiating appropriate therapy. Here, we present two emerging cases of progressive dementia with co-existing serum autoantibodies against the KCNA2 (potassium voltage-gated channel subfamily A member 2) subunit. We found various cognitive deficits with dominant impairments in the memory domain, particularly in delayed recall. One patient presented a subacute onset of then-persisting cognitive deficits, while the other patient's cognitive impairments progressed more chronically and fluctuated. Cognitive impairments coincided with additional neuropsychiatric symptoms. Both had a potential paraneoplastic background according to their medical history and diagnostic results. We discuss the potential role of KCNA2 autoantibodies in these patients and in general by reviewing the literature. The pathogenetic role of KCNA2 antibodies in cognitive impairment is not well delineated; clinical presentations are heterogeneous, and thus a causal link between antibodies remains questionable. Current evidence indicates an intracellular rather than extracellular epitope. We strongly suggest additional prospective studies to explore KCNA2 antibodies in specifically-defined cohorts of cognitively impaired patients via a systematic assessment of clinical, neuropsychological, neuroimaging, as well as laboratory and CSF (cerebrospinal fluid) parameters, and antibody studies to (1) determine the epitope's location (intracellular vs. extracellular), (2) the mode of action, and (3) seek co-existing, novel pathogenetic autoantibodies in sera and CSF.

Case Report: Association of a Variant of Unknown Significance in the FIG4 Gene With Frontotemporal Dementia and Slowly Progressing Motoneuron Disease: A Case Report Depicting Common Challenges in Clinical and Genetic Diagnostics of Rare Neuropsychiatric and Neurologic Disorders.

BACKGROUND: Modern genetics have in many ways revolutionized clinical routine and have, for instance, shown that formerly distinct disease entities relate to common pathogenic mutations. One such example is the connection between dementia and amyotrophic lateral sclerosis (ALS) in a continuous disease spectrum affirmed by the discovery of shared mutations. CASE REPORT: We describe a new variant in the FIG4 gene in a patient with slowly progressing frontotemporal dementia (FTD) and probable primary lateral sclerosis (PLS). The patient initially showed depressive symptoms and global cognitive deficits. Severe difficulties with language and hallucinations became clearer as the disease progressed. Nuclear medicine imaging and cerebrospinal fluid (CSF) biomarkers were not specific for defined categories of dementia, but neuropsychological testing and clinical features finally led to an allocation of the syndrome to the non-fluent variant of primary progressive aphasia (nfv PPA). Because of increasing limb weakness and bulbar symptoms, motoneuron disease in the form of PLS was diagnosed, strongly supported by elevated CSF neurofilament and electrophysiologic assessments. The detected variant in the FIG4 gene is described as pathogenic or likely pathogenic in common databases and reported once in the literature. While the phenotype of our patient fits the description of FIG4-associated disease in literature, we consider the present variant as VUS in this case. CONCLUSION: We describe a variant in the FIG4 gene in a patient with slowly progressing FTD and PLS. Mutations in the FIG4 gene have been associated with ALS and PLS; however, this exact mutation was not reported in ALS or PLS patients before. The case illustrates generic diagnostic challenges in patients presenting with genetic variants that offer an explanation for otherwise uncommon symptom combinations but yet are of unknown significance.

Ultrahigh-field MPRAGE Magnetic Resonance Angiography at 7.0 T in patients with cerebrovascular disease.

OBJECTIVES: Time-of-flight (TOF) magnetic-resonance-angiography (MRA) identifies vessel pathology in cerebrovascular disease. At 7.0 T, the clinical performance of TOF-MRA is constrained owing to radio frequency power deposition. We studied the diagnostic value of whole-brain MPRAGE-based MRA as an alternative imaging technique in comparison to the clinical standard 3.0 T TOF-MRA. METHODS: Patients with stroke and/or moya-moya disease were included. TOF-MRA was performed at 3.0 T and MPRAGE-MRA at 7.0 T. Two radiologists rated the MRAs independently for overall quality and local arterial segment visualization. The identification of steno-occlusive pathology was reported for each protocol. RESULTS: In 18 patients (9 females; 6 patients with moya-moya) 7.0 T MPRAGE-MRA provided better overall image quality and better distinction of small structures compared to 3.0 T TOF-MRA. These findings were pronounced in the proximal segments of the anterior cerebral artery (A1), middle cerebral artery (M1, M2), posterior cerebral artery (P1) and the posterior communicating artery. Seven steno-occlusive findings were identified by both imaging protocols. CONCLUSIONS: For clinical studies using ultrahigh field MRI, 7.0 T MPRAGE-MRA provides a suitable alternative to TOF-MRA imaging to identify brain vessel pathology and yields simultaneous structural brain imaging within clinically feasible acquisition times.

Feasibility of flat panel detector computed tomography for position assessment of external ventricular drainage.

BACKGROUND AND PURPOSE: New angiographic devices with flat panel detectors allow cross-sectional imaging within the angiographic suite. In patients receiving external ventricular drainage (EVD) to manage hydrocephalus following subarachnoid haemorrhage (SAH), these may help evaluating the position of an EVD without moving the patient to a conventional computed tomography (CT) scanner. It could facilitate patients' management in a life-threatening status. This study therefore compares conventional CT with post-interventional flat panel detector angiographic CT (FDCT) referring to the determinability of an accurate EVD position. MATERIAL AND METHODS: Twenty patients with SAH received FDCT and conventional CT for primary assessment after EVD insertion. Three single-blinded raters compared both modalities and evaluated the image sufficiency for determining the EVD position, EVD tip, intracranial course and whether a contorted drainage tube could be detected. RESULTS: FDCT was sufficient to detect a correct EVD position in 82.5% of the cases vs. 100% in conventional CT. Regarding the EVD tip, FDCT delivered at least 'good' results in 82.5% vs. 95% in conventional CT data. Determining the EVD intracranial course, FDCT provided at least 'good' data in 92.5% vs. 100% in conventional CT. For detecting tube contortion, FDCT provided at least 'good' results in 70% vs. 98% in conventional CT. CONCLUSIONS: FDCT is a promising method to determine the correct position of an EVD in patients with SAH. Following a neuroradiological intervention, it facilitates the patients' management and renders additional transfers to conventional CT unnecessary in the majority of cases.

Femoral nerve palsy caused by ileopectineal bursitis after total hip replacement: a case report.

INTRODUCTION: Infectious ileopectineal bursitis is a rare complication after total hip replacement and is associated mainly with rheumatoid arthritis. The main complications are local swelling and pain, but communication of the inflamed bursa with the joint can occur, leading to subsequent cartilage damage and bone destruction. CASE PRESENTATION: We report a case of a 47-year-old Caucasian woman without rheumatoid arthritis who reported pain and palsy in her left leg almost one year after total hip replacement. She was diagnosed with an ileopectineal bursitis after total hip replacement, leading to femoral nerve palsy. The diagnosis was obtained by thorough clinical examination, the results of focused computed tomography and magnetic resonance imaging. CONCLUSION: To the best of our knowledge, this is the first report of non-infectious ileopectineal bursitis in a patient without rheumatoid arthritis as a complication of total hip replacement. This rare case underlines the importance of proper neurologic examination of persistent conditions after orthopedic intervention in otherwise healthy individuals. We believe this case should be useful for a broad spectrum of medical specialties, including orthopedics, neurology, radiology, and general practice.