Attenuation of the BOLD fMRI Signal and Changes in Functional Connectivity Affecting the Whole Brain in Presence of Brain Metastasis.

To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients' FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage.

Limited capability of MRI radiomics to predict primary tumor histology of brain metastases in external validation.

Background: Growing research demonstrates the ability to predict histology or genetic information of various malignancies using radiomic features extracted from imaging data. This study aimed to investigate MRI-based radiomics in predicting the primary tumor of brain metastases through internal and external validation, using oversampling techniques to address the class imbalance. Methods: This IRB-approved retrospective multicenter study included brain metastases from lung cancer, melanoma, breast cancer, colorectal cancer, and a combined heterogenous group of other primary entities (5-class classification). Local data were acquired between 2003 and 2021 from 231 patients (545 metastases). External validation was performed with 82 patients (280 metastases) and 258 patients (809 metastases) from the publicly available Stanford BrainMetShare and the University of California San Francisco Brain Metastases Stereotactic Radiosurgery datasets, respectively. Preprocessing included brain extraction, bias correction, coregistration, intensity normalization, and semi-manual binary tumor segmentation. Two-thousand five hundred and twenty-eight radiomic features were extracted from T1w (±â€…contrast), fluid-attenuated inversion recovery (FLAIR), and wavelet transforms for each sequence (8 decompositions). Random forest classifiers were trained with selected features on original and oversampled data (5-fold cross-validation) and evaluated on internal/external holdout test sets using accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC). Results: Oversampling did not improve the overall unsatisfactory performance on the internal and external test sets. Incorrect data partitioning (oversampling before train/validation/test split) leads to a massive overestimation of model performance. Conclusions: Radiomics models' capability to predict histologic or genomic data from imaging should be critically assessed; external validation is essential.

Detection of virus-specific T cells via ELISpot corroborates early diagnosis in human Borna disease virus 1 (BoDV-1) encephalitis.

BACKGROUND: Within endemic regions in southern and eastern Germany, Borna disease virus 1 (BoDV-1) causes rare zoonotic spill-over infections in humans, leading to encephalitis with a high case-fatality risk. So far, intra-vitam diagnosis has mainly been based on RT-qPCR from cerebrospinal fluid (CSF) and serology, both being associated with diagnostic challenges. Whilst low RNA copy numbers in CSF limit the sensitivity of RT-qPCR from this material, seroconversion often occurs late during the course of the disease. CASE PRESENTATION: Here, we report the new case of a 40 - 50 year-old patient in whom the detection of virus-specific T cells via ELISpot corroborated the diagnosis of BoDV-1 infection. The patient showed a typical course of the disease with prodromal symptoms like fever and headaches 2.5 weeks prior to hospital admission, required mechanical ventilation from day three after hospitalisation and remained in deep coma until death ten days after admission. RESULTS: Infection was first detected by positive RT-qPCR from a CSF sample drawn four days after admission (viral load 890 copies/mL). A positive ELISpot result was obtained from peripheral blood collected on day seven, when virus-specific IgG antibodies were not detectable in serum, possibly due to previous immune adsorption for suspected autoimmune-mediated encephalitis. CONCLUSION: This case demonstrates that BoDV-1 ELISpot serves as additional diagnostic tool even in the first week after hospitalisation of patients with BoDV-1 encephalitis.

SARS-CoV2 evokes structural brain changes resulting in declined executive function.

BACKGROUND: Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus' neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model. METHODS: Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed. RESULTS: Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered. CONCLUSION: Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as 'Post-COVID'.

Targeting the microenvironment in the treatment of arteriovenous malformations.

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31+ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects.

Amelioration of Parkinsonian tremor evoked by DBS: which role play cerebello-(sub)thalamic fiber tracts?

BACKGROUND: Current pathophysiological models of Parkinson's disease (PD) assume a malfunctioning network being adjusted by the DBS signal. As various authors showed a main involvement of the cerebellum within this network, cerebello-cerebral fiber tracts are gaining special interest regarding the mediation of DBS effects. OBJECTIVES: The crossing and non-decussating fibers of the dentato-rubro-thalamic tract (c-DRTT/nd-DRTT) and the subthalamo-ponto-cerebellar tract (SPCT) are thought to build up an integrated network enabling a bidimensional communication between the cerebellum and the basal ganglia. The aim of this study was to investigate the influence of these tracts on clinical control of Parkinsonian tremor evoked by DBS. METHODS: We analyzed 120 electrode contacts from a cohort of 14 patients with tremor-dominant or equivalence-type PD having received bilateral STN-DBS. Probabilistic tractography was performed to depict the c-DRTT, nd-DRTT, and SPCT. Distance maps were calculated for the tracts and correlated to clinical tremor control for each electrode pole. RESULTS: A significant difference between "effective" and "less-effective" contacts was only found for the c-DRTT (p = 0.039), but not for the SPCT, nor the nd-DRTT. In logistic and linear regressions, significant results were also found for the c-DRTT only (pmodel logistic = 0.035, ptract logistic = 0,044; plinear = 0.027). CONCLUSIONS: We found a significant correlation between the distance of the DBS electrode pole to the c-DRTT and the clinical efficacy regarding tremor reduction. The c-DRTT might therefore play a major role in the mechanisms of alleviation of Parkinsonian tremor and could eventually serve as a possible DBS target for tremor-dominant PD in future.

Medical Needs and Therapeutic Options for Melanoma Patients Resistant to Anti-PD-1-Directed Immune Checkpoint Inhibition.

Available 4- and 5-year updates for progression-free and for overall survival demonstrate a lasting clinical benefit for melanoma patients receiving anti-PD-directed immune checkpoint inhibitor therapy. However, at least one-half of the patients either do not respond to therapy or relapse early or late following the initial response to therapy. Little is known about the reasons for primary and/or secondary resistance to immunotherapy and the patterns of relapse. This review, prepared by an interdisciplinary expert panel, describes the assessment of the response and classification of resistance to PD-1 therapy, briefly summarizes the potential mechanisms of resistance, and analyzes the medical needs of and therapeutic options for melanoma patients resistant to immune checkpoint inhibitors. We appraised clinical data from trials in the metastatic, adjuvant and neo-adjuvant settings to tabulate frequencies of resistance. For these three settings, the role of predictive biomarkers for resistance is critically discussed, as well as are multimodal therapeutic options or novel immunotherapeutic approaches which may help patients overcome resistance to immune checkpoint therapy. The lack of suitable biomarkers and the currently modest outcomes of novel therapeutic regimens for overcoming resistance, most of them with a PD-1 backbone, support our recommendation to include as many patients as possible in novel or ongoing clinical trials.

Analysis of Functional Neuroplastic Changes in the Cortical Language System in Relation to Different Growth Patterns of Glioblastoma.

The interpretation of fMRI data in glioblastoma (GB) is challenging as these tumors exhibit specific hemodynamic processes which, together with malignancy, tumor volume and proximity to eloquent cortex areas, may lead to misinterpretations of fMRI signals. The aim of this study was to investigate if different radiologically defined GB tumor growth patterns may also influence the fMRI signal, activation pattern and functional connectivity differently. Sixty-four patients with left-hemispheric glioblastoma were included and stratified according to their radiologically defined tumor growth pattern into groups with a uniform (U-TGP) or diffuse tumor growth pattern (D-TGP). Task-based fMRI data were analyzed using SPM12 with the marsbar, LI and CONN toolboxes. The percent signal change and the laterality index were analyzed, as well as functional connectivity between 23 selected ROIs. Comparisons of both patient groups showed only minor non-significant differences, indicating that the tumor growth pattern is not a relevant influencing factor for fMRI signal. In addition to these results, signal reductions were found in areas that were not affected by the tumor underlining that a GB is not a localized but rather a systemic disease affecting the entire brain.

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.

Case report: A complicated course of Collet-Sicard syndrome after internal carotid artery dissection and lenticulo-striatal artery infarction.

A 40-year-old Caucasian man presented with sudden onset of left-sided hemiparesis associated with dysphonia, dysphagia, and right-sided weakness on shoulder elevation and head rotation. The clinical examination revealed deviation of the tongue to the right, absence of right-sided gag reflex, right-sided palatal and vocal cord paresis, and weakness of the right trapezius and sternocleidomastoid muscles; all were in addition to left-sided brachiocephalic-accentuated hemiparesis. The diagnostic examination revealed dissection of the right carotid artery with occlusion of the middle cerebral artery and infarction in the lenticular-striatal artery territory. Mechanical thrombectomy with stent angioplasty of the right internal carotid artery was performed. The paresis of the left side of the body completely regressed within a week after symptom onset, but the dysphonia, weakness of the right trapezius and sternocleidomastoid muscles, and especially dysphagia persisted and regressed slowly but gradually. The patient required percutaneous gastric tube feeding for the next 12 weeks, possibly because of involvement of subcortical white matter tracts. The constellation of symptoms and clinical findings were consistent with Collet-Sicard syndrome, an extremely rare disorder caused by direct compression of the caudal cranial nerves at the base of the skull.

Clinical Value of Diffusion-Weighted Whole-Body Imaging with Background Body Signal Suppression (DWIBS) for Staging of Patients with Suspected Head and Neck Cancer.

(1) Background: To determine the importance of diffusion-weighted whole-body MRI with background body signal suppression (DWIBS) in the staging process of patients with suspected head and neck carcinomas. (2) Methods: A total of 30 patients (24 male, 6 female) with a median age of 67 years with clinically suspected head and neck carcinoma with pathologic cervical nodal swelling in ultrasound underwent the staging procedure with computed tomography (CT) and whole-body MRI including DWIBS. (3) Results: In a total of 9 patients, abnormalities in the routine work-up of pretherapeutic staging were found. Five cases of either secondary cancer or distant metastases were only visible in DWIBS, while being missed on CT. One diagnosis was only detectable in CT and not in DWIBS, whereas three diagnoses were recognizable in both modalities. (4) Conclusions: DWIBS in addition to a standard neck MRI in cervical lymphadenopathy suspicious for head and neck cancer yielded additional clinically relevant diagnoses in 17% of cases that would have been missed by current staging routine procedures. DWIBS offered a negative predictive value of 98.78% for ruling out distant metastases or secondary malignancies.

[Measuring the cochlea using a tablet-based software package: influence of imaging modality and rater background]. / Vermessung der Cochlea mittels eines Tablet-basierten Softwarepakets: Einfluss der Bildgebungsmodalität und des Untersucherhintergrunds.

BACKGROUND: Cochlear duct length (CDL) is subject to significant individual variation. In the context of cochlear implantation, adapting the electrode array length to the CDL is of potential interest, as it has been associated with improvements in both speech recognition and sound quality. Using a tablet-based software package, it is possible to measure CDL at the level of the organ of Corti (CDLOC) to select appropriate electrode array lengths based on individual cochlear anatomy. OBJECTIVE: To identify effects of imaging modality and rater background on CDL estimates. METHODS: Magnetic resonance imaging (MRI) and flat-panel volume CT (fpVCT) scans of 10 patients (20 cochleae) were analyzed using the OTOPLAN software package (MED-EL, Innsbruck, Austria). Raters were an otorhinolaryngology (ORL) specialist, an ORL resident, and an audiologist. To analyze effects of rater background and imaging modality on CDL measurements, linear mixed models were constructed. RESULTS: Measurements showed mean CDLOC(fpVCT) = 36.69 ± 1.78 mm and CDLOC(MRI) = 36.81 ± 1.87 mm. Analyses indicated no significant effect of rater background (F(2, 105) = 0.84; p = 0.437) on CDL estimates. Imaging modality, on the other hand, significantly affected CDL (F (1, 105) = 20.70; p < 0.001), whereby estimates obtained using MRI were 0.89 mm larger than those obtained using fpVCT. CONCLUSION: No effect of rater background on CDL estimates could be identified, suggesting that comparable measurements could be obtained by personnel other than specially trained neurootologists. While imaging modality (fpVCT vs. MRI) did impact CDL results, the difference was small and of questionable clinical significance.

Validation Study for Non-Invasive Prediction of IDH Mutation Status in Patients with Glioma Using In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning.

The isocitrate dehydrogenase (IDH) mutation status is an indispensable prerequisite for diagnosis of glioma (astrocytoma and oligodendroglioma) according to the WHO classification of brain tumors 2021 and is a potential therapeutic target. Usually, immunohistochemistry followed by sequencing of tumor tissue is performed for this purpose. In clinical routine, however, non-invasive determination of IDH mutation status is desirable in cases where tumor biopsy is not possible and for monitoring neuro-oncological therapies. In a previous publication, we presented reliable prediction of IDH mutation status employing proton magnetic resonance spectroscopy (1H-MRS) on a 3.0 Tesla (T) scanner and machine learning in a prospective cohort of 34 glioma patients. Here, we validated this approach in an independent cohort of 67 patients, for which 1H-MR spectra were acquired at 1.5 T between 2002 and 2007, using the same data analysis approach. Despite different technical conditions, a sensitivity of 82.6% (95% CI, 61.2-95.1%) and a specificity of 72.7% (95% CI, 57.2-85.0%) could be achieved. We concluded that our 1H-MRS based approach can be established in a routine clinical setting with affordable effort and time, independent of technical conditions employed. Therefore, the method provides a non-invasive tool for determining IDH status that is well-applicable in an everyday clinical setting.

Acute Middle Cerebral Artery Occlusion Detection Using Mobile Non-Imaging Brain Perfusion Ultrasound-First Case.

Mobile brain perfusion ultrasound (BPU) is a novel non-imaging technique creating only hemispheric perfusion curves following ultrasound contrast injection and has been specifically designed for early prehospital large vessel occlusion (LVO) stroke identification. We report on the first patient investigated with the SONAS® system, a portable point-of-care ultrasound system for BPU. This patient was admitted into our stroke unit about 12 h following onset of a fluctuating motor aphasia, dysarthria and facial weakness resulting in an NIHSS of 3 to 8. Occlusion of the left middle cerebral artery occlusion was diagnosed by computed tomography angiography. BPU was performed in conjunction with injection of echo-contrast agent to generate hemispheric perfusion curves and in parallel, conventional color-coded sonography (TCCS) assessing MCAO. Both assessments confirmed the results of angiography. Emergency mechanical thrombectomy (MT) achieved complete recanalization (TICI 3) and post-interventional NIHSS of 2 the next day. Telephone follow-up after 2 years found the patient fully active in professional life. Point-of-care BPU is a non-invasive technique especially suitable for prehospital stroke diagnosis for LVO. BPU in conjunction with prehospital stroke scales may enable goal-directed stroke patient placement, i.e., directly to comprehensive stroke centers aiming for MT. Further results of the ongoing phase II study are needed to confirm this finding.

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.

Breakouts-A Radiological Sign of Poor Prognosis in Patients With Brain Metastases.

Purpose: Brain metastases (BM) can present a displacing or infiltrating growth pattern, independent of the primary tumor type. Previous studies have shown that tumor cell infiltration at the macro-metastasis/brain parenchyma interface (MMPI) is correlated with poor outcome. Therefore, a pre-therapeutic, non-invasive detection tool for potential metastatic cell infiltration at the MMPI would be desirable to help identify patients who may benefit from a more aggressive local treatment strategy. The aim of this study was to identify specific magnetic resonance imaging (MRI) patterns at the MMPI in patients with BM and to correlate these patterns with patient outcome. Patients and Methods: In this retrospective analysis of a prospective BM registry, we categorized preoperative MR images of 261 patients with BM according to a prespecified analysis system, which consisted of four MRI contrast enhancement (CE) patterns: two with apparently regularly shaped borders (termed "rim-enhancing" and "spherical") and two with irregular delineation (termed "breakout" and "diffuse"). The primary outcome parameter was overall survival (OS). Additionally analyzed prognostic parameters were the Karnofsky Performance Index, tumor size, edema formation, extent of resection, and RPA class. Results: OS of patients with a breakout pattern was significantly worse than OS of all other groups. Conclusion: Our data show that BM with a breakout pattern have a highly aggressive clinical course. Patients with such a pattern potentially require a more aggressive local and systemic treatment strategy.

Transcranial Doppler sonography and the effect of haematopoietic stem cell transplantation in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is one of the most prevalent monogenetic diseases worldwide and one of the most serious complications is stroke. Transcranial Doppler (TCD) demonstrated to be highly predictive for an imminent stroke by measuring blood flow velocities in the basal cerebral arteries. Currently, the only curative therapy for SCD is hematopoietic stem cell transplantation (HSCT). The aim of this study is to verify the correlation between blood flow velocities and stroke including the effect of HSCT. METHODS: In our retrospective single-center study a total of 26 sickle cell patients (HbSS, HbSß+-thalassemia, HbSSα-thalassemia minima, HbSSα-thalassemia minor and HbSC) were analyzed between 2010 and 2016. The highest time averaged maximum mean blood flow velocity (TAMMV) measured was documented and evaluated with respect to SCD genotype and effect of HSCT. Acute and symptomatic as well as silent strokes were recorded as separate parameters. RESULTS: In our study, ten patients had normal blood flow velocities before HSCT (six HbSS and four HbSß+-thalassemia patients) and 13 patients presented with abnormal TCD (eight HbSS, three HbSSα-thalassemia minima, one HbSSα-thalassemia minor and one HbSC). Thirteen of 26 study participants (ten HbSS and three HbSß+-thalassemia patients) received HSCT. In two patients, TAMMV in basal cerebral arteries remained "normal", in one they remained conditional and in one TAMMV was reduced to normal. Four of 26 study participants (15.4%), including all patients with HbSS genotype, presented with a stroke, but none had "abnormal" TAMMV with TCD performed after the onset of stroke in each case. At the time we performed the TCD, the patients had already suffered the stroke. CONCLUSION: In our study, none of the patients with stroke displayed abnormal blood flow velocities in TCD. Yet, HSCT at this stage of the disease still had a positive effect on TAMMV. Further studies are needed whether this effect converts into reduced stroke risk at all or only selected SCD patients undergoing HSCT.

Recurrent vertebrobasilar strokes and transient-ischemic attacks with challenging workup: Case report.

Detecting the stroke etiology in young patients can be challenging. Among others, determining causality between ischemic stroke and patent foramen ovale (PFO) remains a complicated task for stroke neurologists, given the relatively high prevalence of PFOs. Thorough diagnostic workup to identify incidental vascular risk factors and rare embolic sources is crucial to avoid premature PFO closure suggesting successful secondary stroke prevention. In this paper, we report on a 38-year-old patient with recurrent vertebrobasilar territory, especially right posterior inferior cerebellar artery (PICA) territory strokes. After the initial suspicion of a left vertebral artery (VA) dissection was not confirmed by ultrasound and magnetic resonance imaging (MRI) and other major risk factors were excluded, a PFO was detected and closed. Successful PFO closure was confirmed by transesophageal echocardiography, yet recurrent transient-ischemic attacks and vertebrobasilar strokes, especially during nighttime and in the early morning, occurred despite various antiplatelet and antithrombotic regimes and a persistent right-to-left shunt was detected by bubble transcranial Doppler. Finally, MRI after another vertebrobasilar infarction detected a transient left VA occlusion that finally led to the diagnosis of a left VA pseudoaneurysm from an incident emboligenic dissection in the atlas segment. This pseudoaneurysm together with an anatomical variant of the right PICA originating with the right anterior inferior cerebellar artery from the basilar artery finally explained the recurrent ischemic events of the patient. After successful treatment with coil occlusion, the patient suffered no further stroke and recovered completely. In summary, stroke in the young remains a diagnostic challenge. The incidental finding of a PFO should not deter from thorough stroke workup and the follow-up of these patients including PFO closure verification should be performed under the guidance of vascular neurologists.

Cost-Effectiveness of Endovascular Thrombectomy in Childhood Stroke: An Analysis of the Save ChildS Study.

BACKGROUND AND PURPOSE: The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. METHODS: In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. RESULTS: The model. RESULTS: yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. CONCLUSIONS: EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

Diversion-p64: results from an international, prospective, multicenter, single-arm post-market study to assess the safety and effectiveness of the p64 flow modulation device.

BACKGROUND: The use of flow diversion to treat intracranial aneurysms has increased in recent years. OBJECTIVE: To assess the safety and angiographic efficacy of the p64 flow modulation device. METHODS: Diversion-p64 is an international, prospective, multicenter, single-arm, study conducted at 26 centers. The p64 flow modulation device was used to treat anterior circulation aneurysms between December 2015 and January 2019. The primary safety endpoint was the incidence of major stroke or neurologic death at 3-6 months, with the primary efficacy endpoint being complete aneurysm occlusion (Raymond-Roy Occlusion Classification 1) on follow-up angiography. RESULTS: A total of 420 patients met the eligibility criteria and underwent treatment with the p64 flow modulation device (mean age 55±12.0 years, 86.2% female). Mean aneurysm dome width was 6.99±5.28 mm and neck width 4.47±2.28 mm. Mean number of devices implanted per patient was 1.06±0.47, with adjunctive coiling performed in 14.0% of the cases. At the second angiographic follow-up (mean 375±73 days), available for 343 patients (81.7%), complete aneurysm occlusion was seen in 287 (83.7%) patients. Safety data were available for 413 patients (98.3%) at the first follow-up (mean 145±43 days) with a composite morbidity/mortality rate of 2.42% (n=10). CONCLUSIONS: Diversion-p64 is the largest prospective study using the p64 flow modulation device. The results of this study demonstrate that the device has a high efficacy and carries a low rate of mortality and permanent morbidity.