Search

Purpose: The recently introduced Pipeline Vantage Embolization Device with Shield Technology is the fourth generation of Pipeline flow diverter devices. Due to the relatively high rate of intraprocedural technical complications, modifications were subsequently made to the device after a limited release of the device in 2020. This study aimed to evaluate the safety and efficacy of the modified version of this device., Methods: This was a multicentre retrospective series. The primary efficacy endpoint was aneurysm occlusion in the absence of retreatment. The primary safety endpoint was any neurological morbidity or death. Ruptured and unruptured aneurysms were included in the study., Results: A total of 52 procedures were performed for 60 target aneurysms. Treatment was performed on 5 patients with ruptured aneurysms. The technical success rate was 98%. The mean clinical follow-up time was 5.5 months. In patients presenting with unruptured aneurysms there were no deaths, 3 (6.4%) major complications and 7 (13%) minor complications. In the five patients presenting with subarachnoid haemorrhage there were 2 (40%) major complications with 1 (20%) of these resulting in death, and 1 (20%) minor complication. Of the patients 29 (56%) had undergone 6‑monthly postprocedural angiographic imaging with a mean time of 6.6 months demonstrating that 83% of patients had achieved adequate occlusion (RROC1/2) of the aneurysm., Conclusions: In this non-industry-sponsored study, the occlusion rates and safety outcomes were similar to those seen in previously published studies with flow diverter devices and earlier generation Pipeline devices. Modifications to the device appear to have improved ease of deployment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The Pipeline Vantage Embolization Device (PEDV) is the fourth-generation pipeline flow diverter for intracranial aneurysm treatment. There are no outcome studies for the second PEDV version. We aimed to evaluate safety and efficacy outcomes. Primary and secondary objectives were to determine outcomes for unruptured and ruptured cohorts, respectively., Methods: In this multicenter retrospective and prospective study, we analyzed outcome data from eight centers using core laboratory assessments. We determined 30-day and ≥3-month mortality and morbidity rates, and 6- and 18-month radiographic aneurysm occlusion rates for procedures performed during the period July 2021-March 2023., Results: We included 121 consecutive patients with 131 aneurysms. The adequate occlusion rate for the unruptured cohort at short-term and medium-term follow up, and also for the ruptured cohort at short-term follow up, was >90%. Two aneurysms (1.5%) underwent retreatment. When mortality attributed to a palliative case in the unruptured cohort, or subarachnoid hemorrhage in the ruptured cohort, was excluded then the overall major adverse event rate in respective cohorts was 7.5% and 23.5%, with 0% mortality rates for each. When all event causes were included on an intention-to-treat basis, the major adverse event rates in respective cohorts were 8.3% and 40.9%, with 0.9% and 22.7% mortality rates., Conclusions: For unruptured aneurysm treatment, the second PEDV version appears to have a superior efficacy and similar safety profile to previous-generation PEDs. These are acceptable outcomes in this pragmatic and non-industry-sponsored study. Analysis of ruptured aneurysm outcomes is limited by cohort size. Further prospective studies, particularly for ruptured aneurysms, are needed., Competing Interests: Competing interests: Microvention core laboratory for neurointerventional study: payment to TCB. Siemens Healthineers Speakers Bureau Educational lecture on brain tumours, not related to aneurysms: payment to TCB. Medtronic Speakers Bureau Educational lecture on an independent non-industry-sponsored study published in AJNR 2019 on Pipeline Flow Diverter device: payment to TCB. Bayer Speakers Bureau Educational lecture on Explainability in AI, not related to aneurysms: payment to TCB. Consulting and proctoring agreement with Medtronic, Stryker, Balt, and Cerenovus: payment to TP. Microvention, Balt, and Medtronic support to attend meetings: payment to TM., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Context: Although sleep disordered breathing (SDB) is well-recognised in acromegaly, most studies have reported heterogeneous, often heavily treated, groups and few have performed detailed sleep phenotyping at presentation., Objective: To study SDB using the gold standard of polysomnography, in the largest group of newly-diagnosed, treatment-naïve patients with acromegaly., Setting and Patients: 40 patients [22 males, 18 females; mean age 54 years (range 23-78)], were studied to: (i) establish the prevalence and severity of SDB (ii) assess the reliability of commonly employed screening tools [Epworth Sleepiness Scale (ESS) and overnight oxygen desaturation index (DI)] to detect SDB (iii) determine the extent to which sleep architecture is disrupted., Results: Obstructive sleep apnoea (OSA), defined by the apnoea-hypopnoea index (AHI), was present in 79% of subjects (mild, n = 12; moderate, n = 5; severe, n = 14). However, in these individuals with OSA by AHI criteria, ESS (positive in 35% [n = 11]) and DI (positive in 71%: mild, n = 11; moderate, n = 6; severe, n = 5) markedly underestimated its prevalence/extent. Seventy-eight percent of patients exhibited increased arousal, with marked disruption of the sleep cycle, despite most (82%) having normal total time asleep. Fourteen patients spent longer in stage 1 sleep. Deeper sleep stages were severely attenuated in many subjects (reduced stage 2, n = 18; reduced slow wave sleep, n = 24; reduced rapid eye movement sleep, n = 32)., Conclusion: Our study provides strong support for clinical guidelines that recommend screening for sleep apnoea syndrome in patients with newly-diagnosed acromegaly. Importantly, however, it highlights shortcomings in commonly recommended screening tools (questionnaires, desaturation index) and demonstrates the added value of polysomnography to allow timely detection of obstructive sleep apnoea and associated sleep cycle disruption., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Process Mining is a technique looking into the analysis and mining of existing process flow. On the other hand, Machine Learning is a data science field and a sub-branch of Artificial Intelligence with the main purpose of replicating human behavior through algorithms. The separate application of Process Mining and Machine Learning for healthcare purposes has been widely explored with a various number of published works discussing their use. However, the simultaneous application of Process Mining and Machine Learning algorithms is still a growing field with ongoing studies on its application. This paper proposes a feasible framework where Process Mining and Machine Learning can be used in combination within the healthcare environment.

A previously independent 82-year-old woman presented with 5 months of worsening confusion, mobility and cognitive decline, with deficits in orientation, language and executive function. A cerebral dural arteriovenous fistula was identified and successfully embolised, after which her cognitive ability and independence dramatically improved. Although rare, a dural arteriovenous fistula may mimic a rapidly progressive dementia, but its early recognition and treatment can completely reverse the dementia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Image registration is an inherently ill-posed problem that lacks the constraints needed for a unique mapping between voxels of the two images being registered. As such, one must regularize the registration to achieve physically meaningful transforms. The regularization penalty is usually a function of derivatives of the displacement-vector field and can be calculated either analytically or numerically. The numerical approach, however, is computationally expensive depending on the image size, and therefore a computationally efficient analytical framework has been developed. Using cubic B-splines as the registration transform, we develop a generalized mathematical framework that supports five distinct regularizers: diffusion, curvature, linear elastic, third-order, and total displacement. We validate our approach by comparing each with its numerical counterpart in terms of accuracy. We also provide benchmarking results showing that the analytic solutions run significantly faster-up to two orders of magnitude-than finite differencing based numerical implementations., (© 2021 IOP Publishing Ltd.)

Rare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson's disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.

Background: Surgical clipping of intracranial aneurysms is typically robust and durable. However, residual aneurysmal components may be seen after clipping. Furthermore, there may be occasional aneurysmal recurrence. These factors are both clinically relevant because subarachnoid hemorrhage after clipping is a rare but important event. The rationale for any treatment is to substantially decrease the future risk of hemorrhage. Small series have shown coiling as a retreatment strategy after unsuccessful clipping, but none has explored the feasibility of Woven Endobridge (WEB) implantation., Case Description: We examined the feasibility of WEB implantation as second-line treatment for wide-necked residual aneurysms after unsuccessful clipping. We also recorded the safety and efficacy in this small series of 6 patients. To determine safety, we measured the modified Rankin Scale score before and after the procedure, and at 2 later time points (mean follow-up, 5 months and 15 months). To determine efficacy, we obtained radiographic aneurysm occlusion outcomes (including WEB Occlusion Scale) at these 2 time points. Four middle cerebral artery and 2 anterior communicating artery complex aneurysms were treated with WEB implantation, showing feasibility in 6/6 cases (100%). Follow-up at 15 months showed no change from preprocedural modified Rankin Scale score and there were no other complications. There was adequate occlusion in 5/6 cases (83%)., Conclusions: WEB implantation provided a feasible option in this challenging retreatment scenario. This is a small series and prospective data are required to make outcome inferences for this population. Nonetheless, we observed no complications and high adequate occlusion rates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: The recently introduced Pipeline Flex Embolization Device with Shield Technology (Pipeline Shield) is the third generation of Pipeline flow-diverter devices. It has a new stent-surface modification, which reduces thrombogenicity. We aimed to evaluate clinical and radiographic (safety and efficacy) outcomes of the Pipeline Shield., Materials and Methods: The 30-day and 1-year mortality and morbidity rates and the 6- and 18-month radiographic aneurysm occlusion outcomes for procedures performed between March 2016 and January 2018 were analyzed. 3D-TOF-MRA was used for follow-up., Results: Forty-four attempted Pipeline Shield procedures were performed for 41 patients with 44 target aneurysms (total of 52 aneurysms treated). A total of 88.5% of devices were inserted in the anterior circulation, and 11.5%, in the posterior circulation; 49/52 (94.2%) aneurysms were saccular; and 1/52 (1.9%) was fusiform. One (1.9%) aneurysm was an iatrogenic pseudoaneurysm, and 1 (1.9%) was a dissecting aneurysm. Seventy-one percent (35/49) of the saccular aneurysms were wide-neck (neck, >4 mm), 34.6% (18/52) were large (≥10 mm), and 3.8% (2/52) were giant (≥25 mm). The mean aneurysm sac maximal diameter was 9.0 mm, and the mean neck width was 5.0 mm. The cumulative mortality and morbidity rates were 2.3% and 6.8% at 1 year, respectively. The adequate occlusion rate was 78.8% at 6 months and 90.3% at 18 months., Conclusions: In this pragmatic and non-industry-sponsored study, the occlusion rates and safety outcomes were similar to those seen in previously published studies with flow-diverter devices and earlier generation Pipeline Embolization Devices., (© 2019 by American Journal of Neuroradiology.)

Atypical parkinsonian disorders (APDs) comprise a group of neurodegenerative diseases with heterogeneous clinical and pathological features. Most APDs are sporadic, but rare familial forms have also been reported. Epidemiological and post-mortem studies associated APDs with oxidative stress and cellular protein aggregates. Identifying molecular mechanisms that translate stress into toxic protein aggregation and neurodegeneration in APDs is an active area of research. Recently, ribonucleic acid (RNA) stress granule (SG) pathways were discussed to be pathogenically relevant in several neurodegenerative disorders including APDs. Using whole genome sequencing, mRNA expression analysis, transfection assays and cell imaging, we investigated the genetic and molecular basis of a familial neurodegenerative atypical parkinsonian disorder. We investigated a family with six living members in two generations exhibiting clinical symptoms consistent with atypical parkinsonism. Two affected family members suffered from parkinsonism that was associated with ataxia. Magnetic resonance imaging (MRI) of these patients showed brainstem and cerebellar atrophy. Whole genome sequencing identified a heterozygous stop-gain variant (c.C811T; p.R271X) in the Poly(A) binding protein, cytoplasmic 4-like (PABPC4L) gene, which co-segregated with the disease in the family. In situ hybridization showed that the murine pabpc4l is expressed in several brain regions and in particular in the cerebellum and brainstem. To determine the functional impact of the stop-gain variant in the PABPC4L gene, we investigated the subcellular localization of PABPC4L in heterologous cells. Wild-type PABPC4L protein localized predominantly to the cell nucleus, in contrast to the truncated protein encoded by the stop-gain variant p.R271X, which was found homogeneously throughout the cell. Interestingly, the wild-type, but not the truncated protein localized to RasGAP SH3 domain Binding Protein (G3BP)-labeled cytoplasmic granules in response to oxidative stress induction. This suggests that the PABPC4L variant alters intracellular distribution and possibly the stress granule associated function of the protein, which may underlie APD in this family. In conclusion, we present genetic and molecular evidence supporting the role of a stop-gain PABPC4L variant in a rare familial APD. Our data shows that the variant results in cellular mislocalization and inability of the protein to associate with stress granules.

Background: The introduction of flow-diverting stents in the last decade provides an alternative endovascular treatment choice in selected intracranial aneurysms. This retrospective analysis of a UK centre's experience provides insight into clinical and radiographic outcomes., Methods: Electronic patient records, diagnostic and procedural images and written procedural records for patients treated with the PED between August 2009 and April 2014 were reviewed. Follow-up TOF MRA was performed after treatment. Clinical and radiographic outcomes were analyzed and compared with other PED studies., Results: Twenty-nine patients with 30 attempted PED treatments were reviewed representing 3.5% of the treated aneurysm patient cohort. 63.6% (21/33) of the aneurysms were wide-necked (>4 mm), 60.6% (20/33) were large or giant (≥10 mm). The mean aneurysm sac diameter was 12.0 mm; the mean neck width was 4.5 mm. Mortality and morbidity rates were 3.3% and 10.0%, respectively. The total adequate occlusion rate was 78.1% (25/32) at 18 months. The neck width of aneurysms with residual sac filling and complete occlusion differed significantly (p = 0.04)., Conclusions: Highly selected aneurysms treated with a PED in a UK centre have similar occlusion and complication rates when compared to non-UK studies. Again, it appeared that delayed aneurysm rupture remained a risk for PED treatment in large or giant aneurysms. Follow-up with TOF MRA gave similar occlusion results compared to those obtained with DSA in other studies. The influence of neck size on occlusion rate should be examined in future PED studies.